Abstract

The effects of pentazocine, a weak narcotic-antagonist analgesic, were studied on operant behavior (continuous avoidance schedule), locomotor activity and brain nonoamines in the rat. Operant behavior was increased in a graded manner by 2 to 16 mg/kg of pentazocine and decreased by 32 mg/kg. Both stimulant and depressant effects were antagonized by the potent narcotic antagonist naloxone (8 mg/kg) . Pentazocine, 8 to 64 mg/kg, produced a graded increase in locomotor activity which was not prevented by as much as 16 mg/kg of naloxone. Stimulation of locomotor activity was blocked by α-methyltyrosine, an inhibitor of catecholamine synthesis. The total brain content of norepinephrine, dopamine, and serotonin was reduced by pentazocine; turnover rates were not affected. The depletion of the catecholamines was 2½-3½ times greater than that of serotonin. Morphine, in doses as high as 256 mg/kg, caused a much smaller reduction in brain norepinephrine than did pentazocine and elevated brain levels of dopamine. Naloxone (16 mg/kg) failed to block the effects of pentazocine on brain monoamines but did block those of morphine. These findings have been interpreted as follows: 1) the actions of pentazocine on operant behavior appear to be independent of its effects on brain monoamines; 2) stimulation of locomotor activity by pentazocine may be related to the release of brain monoamines; and 3) some of pentazocine's agonistic effects are mediated by mechanisms distinct from those which mediate the actions of morphine.