We compared the antinociception produced by brief intermittent foot shock (0.8-1.0 mA for 20 sec) and morphine by measuring the peak and duration of the effect, the consequences of spinalectomy and the sensitivity to antagonism by naloxone and d- and l-pentazocine and cyclazocine. Foot shock produced a peak antinociception (FSIA) equal to 10 mg/kg of morphine but the duration of FSIA was much shorter. Naloxone antagonized FSIA but a much larger dose (10 mg/kg) was required than for antagonism of morphine. The d-isomers of pentazocine and cyclazocine reduced FSIA but had no effect on morphine antinociception, whereas the l-isomers increased the peak and duration of FSIA and antagonized morphine-induced antinociception. Spinalectomy, which is known to block morphine antinociception, also blocks FSIA. Foot-shock stress did not produce an increase in tail-flick latency in morphine or methadone-tolerant animals demonstrating cross-tolerance between FSIA and morphine and methadone. The similarities between FSIA and morphine-induced antinociception suggest that similar opioid systems may be involved in both. However, the differences suggest that antinociception produced by brief FSIA involves a nonopiate as well as an opiate mechanism, perhaps with multiple opioid receptor sites having different affinities for the isomers of the antagonists.
Animals Cyclazocine