Earlier studies using brain lesions or drugs that impair 5-hydroxytryptamine (5-HT) neurotransmission suggest that the ascending serotonergic system is involved in behavioral inhibition. Confirming this hypothesis, the present study demonstrates that electrical stimulation of the median raphe nucleus (NMR) of the rat induces behavioral inhibition. Rats implanted with brain electrodes in the NMR were trained to lever press under a variable-interval 1 min schedule of water presentation. At variable time intervals averaging 7 min, periods of 90 sec of brain stimulation were superimposed on VI responding without any exteroceptive stimulus change. Electrical stimulation of the NMR caused suppression of ongoing lever-pressing behavior, proportional to the stimulus intensity. In addition, NMR stimulation elicited defecation, also directly related to the stimulus intensity, and a cluster of somatic and autonomic changes, such as crouching, micturition, piloerection and teeth chattering, that are characteristic of the rat's emotional behavior in stressful situations. In four out of six rats, the response-suppressant effect of NMR stimulation was counteracted by the 5-HT synthesis inhibitor, para-chlorophenylalanine (PCPA), three to five days following the administration of a single dose of 500 mg/kg of the drug. The effect of PCPA tended to disappear after fifteen days and in one rat, was reversed by 5-hydroxytryptophan, given after benserazide, on the third day from PCPA injection. These results support the suggestion that the mesolimbic serotonergic pathway originating in the NMR and projecting to the septal area and the hippocampus is a substrate of behavioral inhibition, in the rat. © 1978.
