Serotonin receptor involvement in the avoidance learning deficit caused by p-chloroamphetamine-induced serotonin release.

The receptor involvement in the p-chloramphetamine (PCA, 2.5 mg kg-1) induced impairment of active avoidance acquisition was examined in the male rat. The avoidance deficit was blocked at low doses by serotonergic (5-HT)-receptor blocking agents but not by alpha-adrenergic-, beta-adrenergic-, opiate-, muscarinic- or dopamine D2-receptor antagonists. The potency of the 5-HT antagonists to block the PCA-induced deficit correlated with their affinity in displacing [3H]ketanserin but not [3H]5-HT binding in the frontal cortex. The potencies of the 5-HT antagonists to block the action of PCA could not be related to their action on muscarinic-, histaminergic H1- or dopaminergic D2-receptor binding in vitro. It is concluded that the avoidance learning deficit caused by PCA-induced 5-HT release is related to activation of 5-HT receptors in the frontal cortex having the characteristics of a 5-HT2 receptor.