AMT catalepsy and hypokinesia: interaction with morphine and cocaine

Acute morphine induced a dose-dependent hypokinesia and rigidity, but only mild and non-dose-dependent catalepsy. AMT, injected 1/2 h after morphine, slightly potentiated catalepsy but not hypokinesia during 3 h after morphine; in contrast, rigidity was decreased. The behavioral changes induced by AMT were accelerated in onset and reached their usual development, although AMT toxicity and hypothermia were completely antagonized; thus, it would appear that AMT hypokinesia/catalepsy are not the consequence of toxicity. When morphine was injected 4 h after AMT, a mutual potentiation of the two drugs on hypokinesia and catalepsy was observed, although previous biochemical measurements had shown no effect of morphine on CA depletion under these conditions. Rigidity appeared to be antagonized. After 17 days of repeated injections, morphine no longer elicited hypokinesia and catalepsy, but no cross-tolerance developed to the AMT behavioral changes. A similar lack of cross-tolerance to the effects of AMT or haloperidol was observed when morphine tolerance was induced by pellet implantation. Catalepsy and hypokinesia developed in a much more pronounced way after two large i.p. doses than after small, multiple administration of AMT; this difference was accompanied by a significantly lower concentration of brain DA, but not NA in the former group. The hyperthermic response observed after a 40 mg/kg s.c. injection of morphine was reversed to hypothermia when the same dose was given 4 or 10 h after CA synthesis inhibition. Cocaine strongly antagonized AMT hypokinesia and catalepsy when given 8 1/2 h after AMT, and, although to a lesser extent, even when injected 12 1/2 h after AMT.