Effects of chronic administration of delta 9-tetrahydrocannabinol on the cardiovascular system, and pressor and behavioral responses to brain stimulation in freely moving rats.

The effects of chronic administration of delta 9-THC on the cardiovascular system, and the pressor and behavioral responses to brain stimulation were investigated in freely moving rats with chronic electrode and arterial cannula implants. delta 9-THC at a dose of 6 mg/kg was injected intraperitoneally once a day for 10 days through an abdominal cannula. On the first day, delta 9-THC induced a significant decrease in heart rate and rise in blood pressure. The animals exhibited abnormal behavior such as catalepsy, walking backward and pivoting. On the 5th day, the bradycardia induced by delta 9-THC markedly decreased and on the 10th day tachycardia was observed. The pressor effect of delta 9-THC significantly increased on the 5th and 10th days. However, delta 9-THC-induced abnormal behavior was observed without any changes following chronic administration. delta 9-THC inhibited the pressor response and behavioral changes to electrical stimulation of the posterior hypothalamus and midbrain reticular formation. No tolerance developed to these depressive effects of delta 9-THC after chronic treatment. These data suggest that tolerance develops only to bradycardic effect of delta 9-THC and that the decrease in vagal activity may play some role in the development of tolerance.