Modulation of the discriminative stimulus effects of cocaine and methamphetamine by the histaminergic system.
The role of the histaminergic system in the discriminative stimulus effects of cocaine and methamphetamine was examined in rats trained to discriminate between saline and cocaine (10 mg/kg) or methamphetamine (1.0 mg/kg). L-histidine (400 mg/kg), a precursor of histamine, significantly enhanced the discriminative stimulus effects of cocaine and methamphetamine. Previous studies have revealed the existence of several histamine receptor types, H1-, H2-, and H3-receptors. These enhancing effects of L-histidine on the discriminative stimulus effects of cocaine and methamphetamine were attenuated by 5.0 mg/kg of pyrilamine (an H1-receptor antagonist), but not by 1.0 mg/kg of zolantidine (an H2-receptor antagonist), suggesting that these enhancing effects of L-histidine were mediated through the activation of H1-receptors. Thioperamide (7.5 mg/kg), an H3-receptor antagonist, also significantly enhanced the discriminative stimulus effects of cocaine and methamphetamine. However, neither pyrilamine nor zolantidine affected the enhancing effects of thioperamide, unlike the results attained with L-histidine. Therefore our findings suggest that the histaminergic system may modify the discriminative stimulus effects of cocaine and methamphetamine mediated through H1- and H3-receptors.
Mori
Tomohisa
T
Department of Toxicology, School of Pharmacy, Hoshi University, Shinagawa-ku, Tokyo, 142-8501 Japan.
Narita
Minoru
M
Onodera
Kenji
K
Suzuki
Tsutomu
T
D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects*; D004357:Drug Synergism; D006632:Histamine / Q000502:physiology*; D006633:Histamine Antagonists / Q000494:pharmacology; D006639:Histidine / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011969:Receptors, Histamine H1 / Q000502:physiology; D018100:Receptors, Histamine H3 / Q000502:physiology
D000697:Central Nervous System Stimulants; D006633:Histamine Antagonists; D010880:Piperidines; D011969:Receptors, Histamine H1; D018100:Receptors, Histamine H3; D008694:Methamphetamine; D006639:Histidine; D006632:Histamine; D003042:Cocaine; C052075:thioperamide