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.
Rassnick
S
S
Department of Pharmacology, Boston University School of Medicine, MA 02118.
Kornetsky
C
C
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006639:Histidine / Q000494:pharmacology*; D007026:Hypothalamic Area, Lateral / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010423:Pentazocine / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D012201:Reward
D006639:Histidine; D010423:Pentazocine