EFFECTS OF DELTA-9-TETRAHYDROCANNABINOL ON THE CARDIOVASCULAR SYSTEM, AND PRESSOR AND BEHAVIORAL RESPONSES TO BRAIN STIMULATION IN RATS

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Effects of delta-9-tetrahydrocannabinol (Δ⁹-THC) on the cardiovascular system, and pressor and behavioral responses to brain stimulation were investigated in rats. In urethane-anesthetized rats, intravenous administration of Δ⁹-THC (1, 2 and 5 mg/kg) produced a significant and transient dose-related rise but no fall in blood pressure. Δ⁹-THC at these doses also produced marked reduction in heart rate which was antagonized by atropine (0.5 mg/kg i.v.) or bilateral vagotomy. In freely moving rats with chronically implanted electrodes and arterial cannula implants, intraperitoneal administration of Δ⁹-THC (4, 6 and 8 mg/kg) induced a rise in blood pressure and marked bradycardia. Abnormal behavior such as catalepsy, walking backwards and pivoting was also observed. Δ⁹-THC failed to inhibit the pressor responses to electrical stimulation of the posterior hypothalamus and midbrain reticular formation, whereas the drug suppressed the behavioral responses to stimulation of both regions. It is concluded that the cardiovascular effects seen with Δ⁹-THC injection are mainly the result of alteration of the efferent vagal activity by acting on the central nervous system and a more potent influence is exerted on the behavioral changes than on autonomic responses to brain stimulation.