Forebrain serotonergic involvement in avoidance learning.

The one-way active avoidance deficit caused by the serotonergic (5-HT) releasing compound p-chloroamphetamine (PCA) was examined in rats after degeneration of 5-HT neurons in the forebrain. Injection of 5,7-dihydroxytryptamine (5,7-DHT) into the forebrain in desipramine (20 mg/kg)-pretreated rats resulted in a 65-70% decrease in 5-HT concentrations in the prefrontal cortex and hippocampus without any significant effect on striatal 5-HT. Slight reductions in noradrenaline (NA) (25%) and dopamine (DA) (34%) concentrations were observed in the prefrontal cortex only. The 5,7-DHT lesions markedly attenuated the impaired avoidance performance induced by PCA (2.5 mg/kg), suggesting that the avoidance deficit depends on intact 5-HT terminals in cortex and/or hippocampus. The 5,7-DHT lesion alone caused a slight but significant impairment of acquisition. The results suggest that 5-HT terminal systems in the forebrain play an important role in avoidance learning.