methamphetamine ( meth ) is a powerful central nervous system ( cns ) stimulant ( 1 ) , which is widely distributed in the human and rat brain ( 2 ) . although meth -dependent individuals often claimed the cognitive and attention - enhancing effect following drug use ( 3 ) , but meth causes dependence and withdrawal syndrome ( 4 ) , long - term changes in the brain structure and function , changes in synaptic plasticity ( 2 ) , cell death via apoptosis ( 5 ) and neurotoxicity ( 3 ) .
however , studies existing about the effects of meth on cognitive functioning , learning and memory are rather inconsistent . for example
, it has been shown that meth -dependence is associated with neurocognitive impairment , including poor attention , learning and memory , episodic memory , and working memory ( 6 - 9 ) . while , other studies in humans ( 10 , 11 ) and animal ( 12 ) models have provided some evidence that meth can improve cognition .
animal studies have also shown that repeated meth exposure impairs learning in the morris water maze in adulthood ; however , prenatal meth exposure improves performance in the retention memory test ( 13 ) , while lower doses of drug did not have any effect on cognition in adult offspring ( 14 ) .
it appears that these discrepancies are due to total dose and duration of drug exposure ( time- dependent effects of meth ) . in the present study , enhanced sensitivity to meth occurred in rats but not dependency .
given that , short ( acute ) and long term ( chronic ) effects of meth exposure ( time- dependent effects of meth ) on the spatial memory performance are unknown in sensitized rats .
thus , we examined the spatial short term ( working ) and long - term ( reference ) memory of meth sensitized rats 30 and 120 min after the injection in the morris water maze . also , reference memory was evaluated after a 30-day period of withdrawal in meth sensitized rats in the morris water maze .
male wistar rats ( 22010 g ) were housed in a 12 hr light / dark cycle at 22 to 24c , with food and water ad libitum .
all of the experimental procedures were conducted in accordance with the national institutes of health s guide for the care and use of laboratory animals .
methamphetamine hydrochloride ( sigma  aldrich , m 8750 ) was dissolved in 0.9% saline .
the rats were chronically treated with subcutaneous injections of meth ( 2 mg / kg ) , once a day for 5 days , as described previously ( 15 ) .
this dose of meth shows no neurotoxicity but produces behavioral sensitization after repeated treatment in rats ( 16 ) .
this experiment examined spatial memory performance of meth sensitized rats 30 and 120 min after the injection of drug . in this experiment ,
38 male rats were divided into four groups ( n=9 - 10 rats per group ) and received saline or meth ( 2 mg / kg , sc , for 5 days ) . all training and testing were conducted 30 or 120 min after injection of meth . considering the half - life of meth in rats approximately 70 min ( 17 , 18 ) , the experimental groups were divided as follows : group 1 : sal exposed / sal 30 min after injection , group 2 : ( sensitive to meth ) meth exposed / meth 30 min after injection , group 3 : sal exposed / sal 120 min after injection , group 4 : meth exposed /meth 120 min after injection . a detailed description of the apparatus and the tracking system has been given in our previous reports ( 19 ) . from day 5 to 10 , all rats were trained in spatial learning ( 4 trials per day for 5 consecutive days ) .
twenty four hours prior to the start of training , rats were allowed to swim 3 min in the pool containing no platform for habituation , as described previously ( 20 , 21 ) .
a spatial probe test was performed 24 hr after the last acquisition session , without platform .
the rats were allowed to swim for 60 sec , and during this period , we recorded the latency to reach the platform location , the time spent in a zone around the platform ( 20 cm radius ) in each quadrant , and the proximity ( the average distance from the center of the platform during the probe test ) and velocity of each animal ( 19 ) .
two days after probe test , training on working memory version of the water maze task was started .
only two trials per day were given for 5 days to stabilize the performance of the animal in task .
final test was performed on day 6 . in the first trial ( acquisition ) , the rat had to find the platform in a new position , the second trial ( retrieval ) was performed 75 min later , as described previously ( 20 ) . in this period , meth injection was performed 30 or 120 min before the acquisition phase .
thus , the total duration of the meth injection was 18 days in experiment 1 .
timelines of experiments thi 
 s experiment examined the effects of meth withdrawal on the spatial reference memory in meth - sensitized rats .
two groups of rats ( saline and methamphetamine - sensitized rats from exp1 ) were exposed to 30 days of spontaneous withdrawal after the end of working memory test .
the experimental groups were divided as follows : group 1 : saline ( sal ) , group 2 : a 30 day period of spontaneous withdrawal ( meth / withd ) .
rats were trained in spatial learning ( 2 trials per day for 3 consecutive days ) .
a spatial probe test was performed 24 hr after the last acquisition session , as described above .
time line ) . the data expressed as the meanstandard error of the mean ( sem ) .
these data were analyzed using two - way analyses of variance ( anova ) , with repeated measures ( day effect , group effect , groupday interaction ) and one -way anova as required .
a student s t - test was used to compare the data between two groups .
male wistar rats ( 22010 g ) were housed in a 12 hr light / dark cycle at 22 to 24c , with food and water ad libitum .
all of the experimental procedures were conducted in accordance with the national institutes of health s guide for the care and use of laboratory animals .
methamphetamine hydrochloride ( sigma  aldrich , m 8750 ) was dissolved in 0.9% saline .
the rats were chronically treated with subcutaneous injections of meth ( 2 mg / kg ) , once a day for 5 days , as described previously ( 15 ) .
this dose of meth shows no neurotoxicity but produces behavioral sensitization after repeated treatment in rats ( 16 ) .
this experiment examined spatial memory performance of meth sensitized rats 30 and 120 min after the injection of drug . in this experiment ,
38 male rats were divided into four groups ( n=9 - 10 rats per group ) and received saline or meth ( 2 mg / kg , sc , for 5 days ) . all training and testing were conducted 30 or 120 min after injection of meth .
considering the half - life of meth in rats approximately 70 min ( 17 , 18 ) , the experimental groups were divided as follows : group 1 : sal exposed / sal 30 min after injection , group 2 : ( sensitive to meth ) meth exposed / meth 30 min after injection , group 3 : sal exposed / sal 120 min after injection , group 4 : meth exposed /meth 120 min after injection . a detailed description of the apparatus and the tracking system has been given in our previous reports ( 19 ) . from day 5 to 10 , all rats were trained in spatial learning ( 4 trials per day for 5 consecutive days ) .
twenty four hours prior to the start of training , rats were allowed to swim 3 min in the pool containing no platform for habituation , as described previously ( 20 , 21 ) .
a spatial probe test was performed 24 hr after the last acquisition session , without platform .
the rats were allowed to swim for 60 sec , and during this period , we recorded the latency to reach the platform location , the time spent in a zone around the platform ( 20 cm radius ) in each quadrant , and the proximity ( the average distance from the center of the platform during the probe test ) and velocity of each animal ( 19 ) .
two days after probe test , training on working memory version of the water maze task was started .
only two trials per day were given for 5 days to stabilize the performance of the animal in task .
final test was performed on day 6 . in the first trial ( acquisition ) , the rat had to find the platform in a new position , the second trial ( retrieval ) was performed 75 min later , as described previously ( 20 ) . in this period ,
thus , the total duration of the meth injection was 18 days in experiment 1 .
timelines of experiments thi 
 s experiment examined the effects of meth withdrawal on the spatial reference memory in meth - sensitized rats .
two groups of rats ( saline and methamphetamine - sensitized rats from exp1 ) were exposed to 30 days of spontaneous withdrawal after the end of working memory test .
the experimental groups were divided as follows : group 1 : saline ( sal ) , group 2 : a 30 day period of spontaneous withdrawal ( meth / withd ) .
rats were trained in spatial learning ( 2 trials per day for 3 consecutive days ) .
a spatial probe test was performed 24 hr after the last acquisition session , as described above .
this experiment examined spatial memory performance of meth sensitized rats 30 and 120 min after the injection of drug . in this experiment ,
38 male rats were divided into four groups ( n=9 - 10 rats per group ) and received saline or meth ( 2 mg / kg , sc , for 5 days ) . all training and testing were conducted 30 or 120 min after injection of meth .
considering the half - life of meth in rats approximately 70 min ( 17 , 18 ) , the experimental groups were divided as follows : group 1 : sal exposed / sal 30 min after injection , group 2 : ( sensitive to meth ) meth exposed / meth 30 min after injection , group 3 : sal exposed / sal 120 min after injection , group 4 : meth exposed /meth 120 min after injection . a detailed description of the apparatus and the tracking system has been given in our previous reports ( 19 ) . from day 5 to 10 , all rats were trained in spatial learning ( 4 trials per day for 5 consecutive days ) .
twenty four hours prior to the start of training , rats were allowed to swim 3 min in the pool containing no platform for habituation , as described previously ( 20 , 21 ) .
a spatial probe test was performed 24 hr after the last acquisition session , without platform .
the rats were allowed to swim for 60 sec , and during this period , we recorded the latency to reach the platform location , the time spent in a zone around the platform ( 20 cm radius ) in each quadrant , and the proximity ( the average distance from the center of the platform during the probe test ) and velocity of each animal ( 19 ) .
two days after probe test , training on working memory version of the water maze task was started .
only two trials per day were given for 5 days to stabilize the performance of the animal in task .
final test was performed on day 6 . in the first trial ( acquisition ) , the rat had to find the platform in a new position , the second trial ( retrieval ) was performed 75 min later , as described previously ( 20 ) . in this period ,
thus , the total duration of the meth injection was 18 days in experiment 1 .
thi 
 s experiment examined the effects of meth withdrawal on the spatial reference memory in meth - sensitized rats .
two groups of rats ( saline and methamphetamine - sensitized rats from exp1 ) were exposed to 30 days of spontaneous withdrawal after the end of working memory test .
the experimental groups were divided as follows : group 1 : saline ( sal ) , group 2 : a 30 day period of spontaneous withdrawal ( meth / withd ) .
rats were trained in spatial learning ( 2 trials per day for 3 consecutive days ) .
a spatial probe test was performed 24 hr after the last acquisition session , as described above .
these data were analyzed using two - way analyses of variance ( anova ) , with repeated measures ( day effect , group effect , groupday interaction ) and one -way anova as required .
a student s t - test was used to compare the data between two groups .
the acquisition data during the 5 days of training in the water maze ( wm ) are illustrated in figure 2 .
two - way analyses of variance ( anova ) , with repeated measures were used to analyze the escape latencies during training .
all groups learned to locate the platform during 5 days of training , as indicated by decreasing escape latencies as training progressed ( f4 , 170=62 .
. statistical analysis showed a significant group effect ( f3 , 34= 206.8 , p= 0.0001 ) and significant interaction between factors ( group day ) ( f12 , 170 = 6.4 , p= 0.0001 ) in the acquisition phase of learning .
the meth groups exhibited significantly higher escape latencies in all 5 days training than those of control group ( p= 0.0001 ) 30 min post injection .
these findings indicated that exposure to meth decreased the learning rate in sensitized groups 30 min post injection .
effect of methamphetamine ( meth ) in acquisition phase of spatial learning in meth - sensitized rats 30 and 120 min after the injection as measured by the wm task .
all groups learned platform location during the 5-day training , except group 30 min after injection of meth .
result showed group of 30 min after injection of meth is not able to learning .   represents a significant different between 30 min after injection of meth and saline groups ( p= 0.0001 ) .  
represents a significant difference between120 min after injection of meth and saline groups on the first day of training ( p= 0.002 ) data related to the distance swam to reach the platform followed similar to the same pattern as the latency .
all groups traveled shorter distances to reach the platform as training progressed ( f4 , 170=42 .
63 , p=0.0001 ) , except meth group 30 min after injection ( data not shown ) .
one -way analyses of variance ( anova ) showed significant effects on the platform location latency between groups ( f3 , 34=410.9 , p=0.0001 ) ( figure 3a ) .
comparisons between groups showed that the mean latency to reach the platform location in sensitized groups were significantly more than those of control groups ( p=0.0001 , p=0.045 ; respectively ) 30 and 120 min after injection of meth , representing the impairment of the spatial reference memory in both groups .
analysis ( figure 3b ) indicate significant difference between groups in time spent in the target ( f3 , 34=35 , p=0.0001 ) , opposite ( f3 , 34=10.34 , p=0.0001 ) and left zones ( f3 , 34=20.9 , p=0.0001 ) .
comparisons between groups showed that the meth groups spent significantly less time in the target zone than those of control groups ( p=0.0001 and p=0.036 , respectively ) 30 and 120 min after injection .
also , meth group spent significantly more time in the opposite zone than those of control groups ( p=0.034 ) 120 min after injection .
effect of methamphetamine ( meth ) on spatial references memory in meth - sensitized rats using the probe trial during the wm task 30 and 120 min after the injection .
( b ) the mean percentage of total time spent in within a zone , with a radius of 20 cm in the target zone or in other zone ( c ) the proximity ( d ) swimming speed of each rat .
results showed that the meth sensitized rats took significantly more time to reach the platform location ( a ) , spent significantly less time in the target zone ( b ) , and had significantly further proximity values ( c ) and also with increased swimming speed compared to their controls ( d ) . in a :   and   indicates a significant different between meth groups compared to their controls ( p=0.0001 , and p=0.045 , respectively ) . in b :   and ^^^indicates a significant different between meth groups compared to their controls ( p=0.0001 , both ) in the target zone .
and ^ indicates a significant different between meth groups compared to their controls ( p=0.024 , and p=0.034 , respectively ) in the opposite zone
.   indicates a significant different between 30 min after injection than those control ( p=0.0001 ) in the left zone . in c :   and   indicates a significant different between meth groups compared to their controls ( p=0.0001 , and p = 0.037 , respectively ) . in d :   and   indicates a significant different between meth groups compared to their controls ( p=0.0001 , and p = 0.003 , respectively ) effect of methamphetamine ( meth ) on acquisition and retention of spatial ( working ) memory in meth - sensitized rats 30 and 120 min after the injection . in acquisition and retention :   and   indicates a significant different between 30 min after injection than those control ( p=0.0001 , both ) figure 3c represents the average proximity to the platform .
a one way anova revealed significant difference between groups ( f3 , 34=78.9 , p=0.0001 ) .
the meth groups had significantly larger average proximity value than control groups ( p=0.0001 , p=0.037 ; respectively ) .
figure 3d showed that both groups had significantly more swim speed than of control groups ( p=0.0001 , p=0.003 , respectively ) .
figure 3 . illustrates the mean escape latencies on the acquisition and retention trials for control and 30 and 120 min after injection of meth .
a one way anova revealed a significant difference between groups in the acquisition ( f3 , 34=13.76 , p=0.0001 ) and retention trials ( f3 , 34=7.95 , p=0.0001 ) .
comparisons between groups showed that the meth groups exhibited significantly higher escape latencies in the acquisition and retention trials than those of control group ( p=0.0001 , both ) 30 min after injection . while , there was not significant difference in the acquisition and retention trials 120 min after injection in the meth groups .
this finding indicates that 120 min after the injection of meth has no effect on either acquisition or retention of working memory in meth -sensitized rats in the water maze .
the data for the spatial reference memory test after prolonged abstinence are shown in figure 5 .
student s t - test indicated that meth -withdrawn rats spent significantly less time in the target zone than those of control group ( t17=6.48 , p=0.0001 ) .
effects of methamphetamine ( meth ) withdrawal on spatial reference memory in meth - sensitized rats using the probe trial during the wm task .
the mean percentage of total time spent in within a zone or in other zone .
results showed that the meth withdrawn rats spent significantly less time in the target zone .  
the acquisition data during the 5 days of training in the water maze ( wm ) are illustrated in figure 2 .
two - way analyses of variance ( anova ) , with repeated measures were used to analyze the escape latencies during training .
all groups learned to locate the platform during 5 days of training , as indicated by decreasing escape latencies as training progressed ( f4 , 170=62 .
. statistical analysis showed a significant group effect ( f3 , 34= 206.8 , p= 0.0001 ) and significant interaction between factors ( group day ) ( f12 , 170 = 6.4 , p= 0.0001 ) in the acquisition phase of learning .
the meth groups exhibited significantly higher escape latencies in all 5 days training than those of control group ( p= 0.0001 ) 30 min post injection .
these findings indicated that exposure to meth decreased the learning rate in sensitized groups 30 min post injection .
effect of methamphetamine ( meth ) in acquisition phase of spatial learning in meth - sensitized rats 30 and 120 min after the injection as measured by the wm task .
all groups learned platform location during the 5-day training , except group 30 min after injection of meth .
result showed group of 30 min after injection of meth is not able to learning .   represents a significant different between 30 min after injection of meth and saline groups ( p= 0.0001 ) .  
represents a significant difference between120 min after injection of meth and saline groups on the first day of training ( p= 0.002 ) data related to the distance swam to reach the platform followed similar to the same pattern as the latency .
all groups traveled shorter distances to reach the platform as training progressed ( f4 , 170=42 .
63 , p=0.0001 ) , except meth group 30 min after injection ( data not shown ) .
one -way analyses of variance ( anova ) showed significant effects on the platform location latency between groups ( f3 , 34=410.9 , p=0.0001 ) ( figure 3a ) .
comparisons between groups showed that the mean latency to reach the platform location in sensitized groups were significantly more than those of control groups ( p=0.0001 , p=0.045 ; respectively ) 30 and 120 min after injection of meth , representing the impairment of the spatial reference memory in both groups .
analysis ( figure 3b ) indicate significant difference between groups in time spent in the target ( f3 , 34=35 , p=0.0001 ) , opposite ( f3 , 34=10.34 , p=0.0001 ) and left zones ( f3 , 34=20.9 , p=0.0001 ) .
comparisons between groups showed that the meth groups spent significantly less time in the target zone than those of control groups ( p=0.0001 and p=0.036 , respectively ) 30 and 120 min after injection .
also , meth group spent significantly more time in the opposite zone than those of control groups ( p=0.034 ) 120 min after injection .
effect of methamphetamine ( meth ) on spatial references memory in meth - sensitized rats using the probe trial during the wm task 30 and 120 min after the injection .
( b ) the mean percentage of total time spent in within a zone , with a radius of 20 cm in the target zone or in other zone ( c ) the proximity ( d ) swimming speed of each rat .
results showed that the meth sensitized rats took significantly more time to reach the platform location ( a ) , spent significantly less time in the target zone ( b ) , and had significantly further proximity values ( c ) and also with increased swimming speed compared to their controls ( d ) . in a :   and   indicates a significant different between meth groups compared to their controls ( p=0.0001 , and p=0.045 , respectively ) . in b :   and ^^^indicates a significant different between meth groups compared to their controls ( p=0.0001 , both ) in the target zone .
and ^ indicates a significant different between meth groups compared to their controls ( p=0.024 , and p=0.034 , respectively ) in the opposite zone .  
indicates a significant different between 30 min after injection than those control ( p=0.0001 ) in the left zone . in c :   and   indicates a significant different between meth groups compared to their controls ( p=0.0001 , and p = 0.037 , respectively ) . in d :   and   indicates a significant different between meth groups compared to their controls ( p=0.0001 , and p = 0.003 , respectively ) effect of methamphetamine ( meth ) on acquisition and retention of spatial ( working ) memory in meth - sensitized rats 30 and 120 min after the injection . in acquisition and retention :   and   indicates a significant different between 30 min after injection than those control ( p=0.0001 , both ) figure 3c represents the average proximity to the platform .
a one way anova revealed significant difference between groups ( f3 , 34=78.9 , p=0.0001 ) .
the meth groups had significantly larger average proximity value than control groups ( p=0.0001 , p=0.037 ; respectively ) .
figure 3d showed that both groups had significantly more swim speed than of control groups ( p=0.0001 , p=0.003 , respectively ) .
figure 3 . illustrates the mean escape latencies on the acquisition and retention trials for control and 30 and 120 min after injection of meth . a one way anova revealed a significant difference between groups in the acquisition ( f3 , 34=13.76 , p=0.0001 ) and retention trials ( f3 , 34=7.95 , p=0.0001 ) .
comparisons between groups showed that the meth groups exhibited significantly higher escape latencies in the acquisition and retention trials than those of control group ( p=0.0001 , both ) 30 min after injection . while , there was not significant difference in the acquisition and retention trials 120 min after injection in the meth groups .
this finding indicates that 120 min after the injection of meth has no effect on either acquisition or retention of working memory in meth -sensitized rats in the water maze .
the data for the spatial reference memory test after prolonged abstinence are shown in figure 5 .
student s t - test indicated that meth -withdrawn rats spent significantly less time in the target zone than those of control group ( t17=6.48 , p=0.0001 ) .
effects of methamphetamine ( meth ) withdrawal on spatial reference memory in meth - sensitized rats using the probe trial during the wm task .
the mean percentage of total time spent in within a zone or in other zone .
results showed that the meth withdrawn rats spent significantly less time in the target zone .  
we found that meth - sensitized rats showed spatial working and reference memory impairment 30 min after injection of meth .
furthermore , rats did not show impairment of learning ability in reference memory and the acquisition and retention of working memory 120 min after drug injection in meth- sensitized rats , but the retention of spatial reference memory in the wm task is impaired .
thus , the spatial learning and memory deficits observed in the sensitized rats 30 min after injection could potentially be interpreted as an acute effect of meth , which is associated with increased levels of anxiety and aggressive behavior ( 13 , 22 , 23 ) . in our study ,
aggressive behavior was evident 30 min after injection , whereas it is clearly decreased 120 min after injection of the drug in the sensitized rats ; probably because of the half - life of meth that is 70 min in rats ( 17 , 18 ) .
thus , drug sensitivity -induced anxiety and aggressive behaviors were increased after 30 min of injection in meth- sensitized rats and decreased during 120 min after injection .
it seems that stress is reduced 120 min after injection during training of water maze , which facilitated spatial learning .
also , we observed that almost all rats spend most of their time during trials training in the peripheral regions of the quadrant 30 min after injection .
thus , despite the high swimming speed 30 min after injection , the learning has not occurred and rats failed to find the hidden platform .
this finding is consistent with previous results showing that methamphetamine increases locomotor activity ( 24 ) .
the mechanism(s ) underlying the spatial learning and memory deficits following meth ( 30 min after the drug injection ) are unknown . although it seems , stress - related pathways , the creatine system and monoamine levels in brain may be involved . since it was shown that acute administration of meth after a single dose increased corticosterone , and hyperthermia and decreased hippocampal 5-ht levels and the brain creatine that affect cognitive function ( 25 ) .
also , we observed that the intensity of impairment is low 120 min after injection compared to 30 min after injection of drug ( this was statistically significant ) .
therefore , another explanation is that 120 min after injection may be interpreted as residual drug effects of chronic and rats developed tolerance to the methamphetamine and may have resulted in a reduction in drug efficacy ; so , the intensity of impairment was low ; however , there was statistically significant difference as compared to the saline group . in line with our study
, it was shown that neonatal treatment with meth had no effect on working memory ( 26 ) .
another study has shown that prenatal exposure to higher doses of meth ( 15 , 20 mg / kg ) induced impairments of spatial memory in the mwm tested in adulthood ( 14 ) . while , in our study dose of 2 mg / kg induced impairment of spatial long - term memory .
this difference may be due to the duration and timing of drug injection during pregnancy ( 27 ) .
also , we found that after prolonged abstinence , rats exhibited a deficit in spatial reference memory .
our findings is in accordance with those reported in previous studies ( 28 , 29 ) .
although the mechanism that underlies the impairing effects of meth after prolonged abstinence is unknown , it has been suggested that chronic meth may lead to the neurodegeneration ( 30 ) apoptosis ( 5 ) and reduction of ltp ( 2 ) in neurons of the hippocampus .
meth administration results in long lasting dopamine depletion in humans and animals ( 31 ) .
it is probable that the degenerative effects of meth have been sustained even after prolonged abstinence in the hippocampus .
therefore , we found that rats showed spatial memory deficits after 30 days of withdrawal .
our findings indicate that drug sensitivity was increased 30 min after injection in methamphe - tamine -sensitized rats , thus leading to the destruction of learning and memory . so that 120 min after injection of meth in sensitized rats did not impair learning ability and working memory , but partially impaired retention of spatial reference memory , which persisted even after prolonged abstinence of drug .
 objective(s):there is controversial evidence about the effect of methamphetamine ( meth ) on spatial memory . 
 we tested the time- dependent effects of meth on spatial short - term ( working ) and long - term ( reference ) memory in meth sensitized and withdrawn rats in the morris water maze.materials and methods : rats were sensitized to meth ( 2 mg / kg , daily/5 days , sc ) . 
 rats were trained in water maze ( 4 trials / day / for 5 days ) . 
 probe test was performed 24 hr after training . 
 two days after probe test , working memory training ( 2 trials / day / for 5 days ) was conducted . 
 acquisition  
 retention interval was 75 min . 
 the treatment was continued per day 30 and 120 min before the test . 
 two groups of meth sensitized rats were trained in reference memory after a longer period of withdrawal ( 30 days).results : sensitized rats exhibited significantly longer escape latencies on the training , spent significantly less time in the target zone ( all , p<0.05 ) , and their working memory impaired 30 min after injection . while , meth has no effect on the spatial learning process 120 min after injection , and rats spent significantly less time in the target zone ( p<0.05 ) , as well it has no effect on working memory . also , 
 impairment of reference memory persisted after prolonged abstinence.conclusion:our findings indicated that meth impaired spatial learning and memory 30 min after injection , but spared spatial learning , either acquisition or retention of spatial working , but partially impaired retention of spatial reference memory following 120 min after injection in sensitized rats , which persisted even after prolonged abstinence . 
Introduction
Materials and Methods
Animals and induction of methamphetamine- induced sensitization
Experimental protocols
Experiment 1: Reference memory and working memory testing using the water maze
Experiment 2: Reference memory testing after a 30-day period of withdrawal in METH sensitized rats
Statistical analysis
Results
Spatial learning
Spatial reference memory
Spatial working memory
Spatial learning and reference memory after a withdrawal period of METH
Discussion
Conclusion