Changes in locomotor activity, core temperature, and heart rate in response to repeated cocaine administration.

The effects of daily single injections of 20 mg/kg cocaine on locomotor activity, core temperature, and heart rate were determined by radiotelemetry. There was a progressive increase in locomotor activity over the 30-day treatment period. Cocaine-induced activity was 9-12-fold greater than that of saline-treated animals. Cocaine also caused increases in core temperature and heart rate. Tolerance did not develop to the locomotor, hyperthermic, and tachycardic responses resulting from repeated cocaine administration. Comparison of the time-course of the cocaine-induced responses revealed that, on Day 1 and 3, the peak locomotor activity was observed 15 min after cocaine administration, whereas the hyperthermic response peaked at 95 min on those days. The fact that the peak locomotor activity and the hyperthermic response occurred at different times suggests that different processes acting independently or interacting may be involved in these actions of cocaine.

Effects of calcium channel entry blockers on cocaine and amphetamine-induced motor activities and toxicities.

The effects of calcium channel entry blockers on cocaine and amphetamine-induced behavioral responses were investigated. Cocaine and amphetamine produced dose-dependent increases in locomotor activity and stereotyped behavior with a maximum response at 40 and 1.2 mg/kg, respectively. The 1,4-dihydropyridine nimodipine and the benzothiazepine diltiazem were more effective in inhibiting cocaine (20 mg/kg)-induced responses than amphetamine (0.6 mg/kg)-induced responses. At doses of cocaine and amphetamine that caused seizures and death, nimodipine, nitrendipine and diltiazem did not offer any protection; rather, they potentiated the toxicities produced by these psychomotor stimulants.

Effects of alpha-2-adrenoceptor agonists on induced diuresis in rats.

The alpha-2 adrenoceptor agonists, clonidine, guanabenz, and guanfacine, injected subcutaneously produced a dose-related diuresis. The maximal effect occurred at 2h after administration of clonidine 192 micrograms/kg or 960 micrograms/kg of guanabenz and guanfacine. The alpha-2 antagonist, yohimbine, in doses of 1-8 mg/kg administered prior to the agonists caused a dose-dependent decrease in urine output. The action of the three agonists at alpha-2 adrenoceptors was supported by the observation that the alpha-1 adrenoceptor agonist, prazosin (0.61-2.5 mg/kg), administered prior to each agonist caused an inconsistent decrease in the elevated urinary output caused by clonidine, guanabenz and guanfacine. These results indicate that stimulation of alpha-2 adrenoceptors causes diuresis in the rat.

Effect of crowding on amphetamine-induced disaggregation of brain polyribosomes.

DL-amphetamine's actions on brain polyribosomes were studied in crowded and uncrowded mice. The administration of 20 mg/kg DL-amphetamine induced disaggregation of brain polyribosomes in both crowded and uncrowded mice 30 min post drug administration. However, the magnitude of polysome dissociation was observed to be greater in crowded animals than in uncrowded ones. In studying the dose-response relationship there appears to be a relationship between drug dose and polysome disaggregation in both groups of animals, although the effects were always greater in crowded mice. The magnitude of polysome dissociation appears to parallel both in the intensity of central nervous system stimulation, and degree of crowding. Haloperidol was able to block the increased locomotor activity due to drug dose and crowding at 1 mg/kg, and significatnly suppress disaggregation of brain polysomes in crowded animals. A possible role of the effects of crowding on the central nervous system in the presence of amphetamine as it relates to polysome dissociation has been presented.