Irritable aggression induced by delta 9-tetrahydrocannabinol in rats pretreated with 6-hydroxydopamine.

Administration of delta 9-tetrahydrocannabinol (THC) to grouped rats injected intraventricularly with 6-hydroxydopamine (6-OHDA) produced violent fighting accompanied by remarkable hyperirritability. This behavior was induced reproducibly from the 10th to 100th postoperative days. It was shown that this irritable aggression could be measured continuously and quantitatively in terms of degree of activity and/or vocalization using a newly designed analyzer. The effect of THC differed markedly from the action of apomorphine and methamphetamine in 6-OHDA pretreated rats. Apomorphine induced irritable aggression but not vigorous vocalization. On the other hand, methamphetamine induced much less irritable aggression than apomorphine-induced aggression. It is assumed that a THC-invoked imbalance in catecholamine agonistic and serotonin antagonistic action brought about by activation of supersensitized catecholaminergic receptor was operating to produce the aggression. Specifically, hypoactivity of serotonergic neurons might play a key role in the occurrence of THC-induced irritable aggression.