Increased sensitivity to intracerebroventricular infusion of serotonin and deaminated indoles after lesioning rat with dihydroxytryptamine

Rats were prepared with a chronic intracerebroventricular cannula, and treated with intracisternal 5,7-dihydroxytryptamine (DHT) after i.p. desmethylimipramine or control vehicle. After recovery, they were tested behaviorally by direct observation and electronic monitoring of motor activity. Intraventricular infusion of a placebo or 5-hydroxyindoleacetic acid (5-HIAA) had little effect, but serotonin (5-HT) decreased, and norepinephrine increased locomotor activity in intact rats. Following pretreatment with 5,7-DHT, a small increase in locomotor activity was noted which was not altered by intracranial infusion of vehicle. In contrast, infusions of 5-HT produced a striking dose-dependent (ED50 = 5 micrograms/min) pattern of hyperactivity, 'myoclonic' jerking movements, postural changes, and autonomic responses. Norepinephrine increased locomotor activity in the DHT-lesioned rats (but not significantly more than in controls), but failed to produce the myoclonic syndrome. The deaminated indoles, indoleacetaldehyde and 5-HIAA were more potent than 5-HT in producing the myoclonic response; tryptamine when infused at an equimolar dose had no effect. The putative serotonin antagonists, cyproheptadine and methiothepin (i.p.), were more effective in blocking responses to infused 5-HT than to equipotent doses of deaminated indoles. These behavioral responses may represent exaggerated ex"itatory effects mediated by serotonin in the brain stem and spinal cord, possibly modified by altered forebrain mechanisms. A neurophysiologic or neuropharmacologic role for deminated indoles should be reconsidered as they may not merely be inactive metabolites.