Histaminergic receptors of medial septum and conditioned place preference: D1 dopamine receptor mechanism

In the present study, the effects of intra-medial septum injections of histamine and/or the histamine H1 or H2 receptor antagonists on the acquisition of conditioned place preference (CPP) in male Wistar rats have been investigated. Our data showed that the conditioning treatments with intra-medial septum injection of different doses of histamine (0.5–15 μg/rat) induced a significant CPP for the drug-associated place. Using a 3-day schedule of conditioning, it was found that the histamine H1 receptor antagonist, pyrilamine (10 and 15 μg/rat, intra-medial septum) also induced a significant place preference. In addition, pyrilamine inhibited the histamine (7.5 μg/rat)-induced place preference. Intra-medial septum administration of the histamine H2 receptor antagonist, ranitidine (5–15 μg/rat) alone or in combination with histamine did not produce a significant place preference or place aversion. On the other hand, intra-medial septum administration of the dopamine D1 receptor antagonist, SCH 233390 (0.5, 0.75 and 1 μg/rat) inhibited the histamine (7.5 μg/rat) or pyrilamine (15 μg/rat)-induced place preference in a dose-dependent manner, but no effect was observed for the dopamine D2 receptor antagonist, sulpiride on the histamine or pyrilamine response. The administration of histamine (2.5–15 μg/rat) or pyrilamine (10 and 15 μg/rat) during acquisition increased locomotor activity of the animals on the testing days. The results suggest that histaminergic receptors of the medial septum may be involved in CPP and thus it is postulated that dopamine D1 receptors may play an important role in this effect.