Tsutomu Suzuki1, Tomohisa Mori2, Minoru Tsuji2,
Mutsuko Nomura2, Miwa Misawa2 and Kenji Onodera3
1Department of Toxicology, School of Pharmacy, Hoshi University, Shinagawa-ku, Tokyo 142 - 8501, Japan
2Department of Pharmacology, School of Pharmacy, Hoshi University, Shinagawa-ku, Tokyo 142 - 8501, Japan
3Department of Pharmacology, Tohoku University School of Dentistry, 4 - 1 Seiryo-machi, Aobaku, Sendai 980 - 8575, Japan
Abstract: The place preferences by some histamine H1 antagonists, such as tripelennamine, optical isomers of chlorpheniramine (dl-, d- and l-forms) and pyrilamine, in rats were evaluated with the conditioned place preference paradigm. In the present study, tripelennamine and all of the optical isomers of chlorpheniramine, but not pyrilamine, produced a significant place preference. The degree of the place preference induced by optical isomers of chlorpheniramine (6.0 mg/kg) did not correlate with the H1-antagonistic potency of these drugs, suggesting that H1-antagonist-induced place preferences are not mediated by H1-receptor blockade. The tripelennamine (3.0 mg/kg)- and dl-chlorpheniramine (6.0 mg/kg)-induced place preferences were completely abolished by pretreatment with the dopamine D1-receptor antagonist SCH23390 (0.05 mg/kg). Furthermore, the doses of H1 antagonists that induced a place preference significantly reduced the levels of DOPAC, which may be mediated by inhibition of dopamine uptake, in the limbic forebrain (including the nucleus accumbens and olfactory tubercle). These results suggest that some H1 antagonists induce rewarding effects, which may be mediated by the activation of dopamine D1 receptors, followed by the inhibition of dopamine uptake.
Keywords: H1 antagonist, Conditioned place preference, Dopamine uptake inhibition,
Dopamine D1 receptor