Histamine H(1) antagonist treatment with pyrilamine reduces nicotine self-administration in rats.
Nicotine has been definitively shown to be critically involved in the neural bases of tobacco addiction. However, nicotine releases a wide variety of neurotransmitters. Nicotine-induced dopamine release has been shown to play a key role in facilitating nicotine self-administration. Other transmitter systems may also play important roles in the pharmacological effects of nicotine and may provide important leads for combating nicotine self-administration. Clozapine, an antipsychotic drug, which blocks a variety of different transmitter receptors including serotonin 5HT(2) and histamine H(1) receptors, has been found to decrease smoking. Previously we found that the serotonin 5HT(2) antagonist, ketanserin, significantly reduced nicotine self-administration. In the current study, we assessed histamine H(1) receptor interaction with nicotine self-administration. Young adult female Sprague-Dawley rats were fitted with IV catheters and trained to self-administer nicotine (0.03mg/kg/infusion). Acute doses of 40mg/kg of pyrilamine, a histamine H(1) antagonist, significantly reduced nicotine self-administration. We also found that repeated injections (20mg/kg) or chronic infusion via osmotic minipumps (50mg/kg/day) of pyrilamine also significantly decreased nicotine self-administration. The peripherally restricted H(1) antagonist ebastine was ineffective in reducing nicotine self-administration, pointing to central H(1) receptor blockade as key for the effectiveness of pyrilamine. H(1) antagonists may be a promising avenue to explore for new treatments to aid smoking cessation.
Department of Psychiatry and Behavioral Sciences, Box #104790, Duke University Medical Center, Durham, NC 27710, USA. edlevin@duke.edu
Edward D
ED
Levin
Susan
S
Slade
Corinne
C
Wells
Margaret
M
Pruitt
Vanessa
V
Cousins
Marty
M
Cauley
Ann
A
Petro
Dawn
D
Hampton
Jed
J
Rose
D000818:Animals; D002090:Butyrophenones / Q000494:pharmacology; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005502:Food; D006632:Histamine / Q000378:metabolism*; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007260:Infusion Pumps; D007267:Injections; D009042:Motivation / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011738:Pyrilamine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000378:metabolism
D002090:Butyrophenones; D006634:Histamine H1 Antagonists; D010880:Piperidines; D009538:Nicotine; D006632:Histamine; D011738:Pyrilamine; C058249:ebastine