Increased tilt-cage activity after serotonin depletion by 5,7-dihydroxytryptamine

Administration of 5,7-dihydroxytryptamine (5,7-DHT, 8 μg) into the medial forebrain bundle produced a 78% decrease in forebrain serotonin (5-HT) and a 2-fold increase in 24 hr tilt-cage activity. Intraventricular administration of 5.7-DHT (200 μg) resulted in a 4-fold increase in 24 hr activity and 5-HT depletions of 83%, 58% and 71% in forebrain, brainstem and spinal cord, respectively. The diurnal index of activity was identical for 5,7-DHT and control groups, suggesting preservation of the normal light-dark activity rhythm which contrasts with the disruption of this rhythm reported in p-chlorophenylalanine ( p-CPA)-induced hyperactivity. Furthermore, unlike rats with median raphe lesions, 5,7-DHT-treated-rats were hypoactive when tested in the open-field. Administration of p-CPA produced a dose-dependent increase in tilt-cage activity in normal rats, but had relatively little effect on activity in 5,7-DHT-treated-rats. It is concluded that different methods of 5-HT depletion can result in different effects on various behavioral measures, but that this does not appear to be the case for tilt-cage hyperactivity. That is, this effect occurs following electrolytic raphe lesions, p-CPA or 5,7-DHT. It is, therefore, suggested that this effect is not the result of non-specific damage but rather is due to subnormal 5-HT synaptic activity in the central nervous system.