L-histidine attenuates the effects of pentazocine on rewarding brain-stimulation

Previous research has indicated that the antihistamine tripelennamine potentiates the threshold lowering effects of pentazocine on brain stimulation reward, a model of drug-induced euphoria. To determine the importance of histamine in this interaction, we studied the effects of co-administration of L-histidine and pentazocine on the threshold for brain stimulation reward. Pentazocine (2.5-10.0 mg/kg) lowered the threshold for rewarding stimulation to the medial forebrain bundle-lateral hypothalamus in male F344 rats. L-histidine (500 and 750 mg/kg) by itself had no significant effects, yet antagonized the threshold lowering effects of pentazocine. These doses of L-histidine are known to significantly raise brain histamine concentrations. Our results suggest that histamine may play a tonic inhibitory role, at least in part, on the neural systems responsible for the reinforcing properties of pentazocine.