glands. crh also stimulates the release of neurotransmitter in the hypothalamic regions of the brain to mediate stress-induced changes in brain activity this system plays a key role in the reinstatement of conditioned place preference. crh acts as a neurotransmitter in regions of the brain including the bed nucleus of the stria terminalis and the amygdala. reinstatement of conditioned place preference has shown to be blocked when antagonists for crh receptors are injected into the bnst. in other words, the effects of stress on reinstatement can be inhibited by blocking the receptor sites for crh in certain areas of the brain. the neurotransmitter noradrenaline also plays a role in stress-induced reinstatement. blockage of certain noradrenergic receptors inhibit stress-induced reinstatement. furthermore, disinhibition of areas of the brain which inhibit the release of noradrenaline also nullifies the effect of stress-induced reinstatement. together, the noradrenaline and crh systems play a key role in the stress-induced reinstatement of conditioned place preference and provide knowledge of the neurochemical basis of stress-induced relapse. relapse research on stress and drug-primed reinstatement has implications for the treatment of addiction research in humans. reinstatement studies on stress and drug primes provide evidence for their role in relapse behavior in humans. in addition to conditioned placed preference, animal testing using self-administration procedures have also been used to examine potential causes of relapse in humans. stress and drug-primes have also shown to contribute to relapse behaviour in humans. with the knowledge that stress and drug primes contribute to relapse behavior, measures to avoid stressful situations can help addicts avoid returning to their addictive behaviors. drug priming is thought to induce relapse in humans because of its effects on the reward circuits of the brain. repeated drug exposure is thought to sensitize the rewarding effect of the drug and exposure to the drug after extinction can reintroduce this rewarding effect. these effects play a key role in the persistence of drug-seeking behaviors. researchers use the reinstatement procedure to test the ability of certain drugs to inhibit these different types of reinstatement. one such drug that has been shown to have attenuating effects on reinstatement is mecamylamine. this is a selective nicotinic acetylcholine receptor antagonist which, if administered after extinction trials, can block the reinstatement of the conditioned place preference for nicotine and opiates. although direct causal linkages cannot be assumed between reinstatement in the conditioned place preference procedure and relapse in humans, it provides a solid first step in the process of creating drugs that may one day be used to treat relapse in humans. knockout mice knockout mice are used to demonstrate behavioural or physiological differences knockout mice are genetically modified mice that have had certain genes selectively removed. the removal of certain genes allows researchers to study the effects of certain genes missing and the implications of missing genes on physiology and behaviour. cocaine genetic knockouts of the dopamine transporter failed to eliminate the conditioned place preference of cocaine, implying there may be different mechanisms of cocaine's reinforcing properties. mice lacking the noradrenaline transporter and serotonin transporter separately or at the same time demonstrated an enhanced conditioned place preference. no conditioned place preference was found in knockout mice lacking serotonin receptor 5-ht1b. nicotine genetic knockouts of nicotinic receptor subunit β2 in mice resulted in a lack of conditioned place preference. this further compiling information of the importance of the nachr subunit β2 in nicotine's reinforcing properties. studies also show a lack of conditioned place preference in cb1 receptor knockout mice, implicating a possible contribution of the endocannabinoid system. ethanol genetic knockouts of the dopamine d2 receptor and vesicular monoamine transport 2 (vmat2) exhibited a lack of conditioned place preference. mice lacking the mu opioid receptor exhibited a lack of conditioned place preference. knockouts of cb1 cannabinoid receptor demonstrated a lack of conditioned place preference. ethanol appears to have a widespread action on the brain through the many different mechanisms of the drug.