Acute and chronic interactive treatments of serotonin 5HT(2C) and dopamine D-1 receptor systems for decreasing nicotine self-administration in female rats

摘要

A variety of neural systems are involved in the brain bases of tobacco addiction. Animal models of nicotine addiction have helped identify a variety of interacting neural systems involved in the pathophysiology of tobacco addiction. We and others have found that drug treatments affecting many of those neurotransmitter systems significantly decrease nicotine self-administration. These treatments include dopamine D-1 receptor antagonist, histamine H1 antagonist, serotonin 5HT(2c) agonist, glutamate NMDA antagonist, nicotinic cholinergic alpha 4 beta 2 partial agonist and nicotinic cholinergic alpha 3 beta 4 antagonist acting drugs. It may be the case that combining treatments that affect different neural systems underlying addiction may be more efficacious than single drug treatment. In the current study, we tested the interactions of the D-1 antagonist SCH-23390 and the serotonin 5HT(2c) agonist lorcaserin, both of which we have previously shown to significantly reduce nicotine self-administration. In the acute interactions study, both SCH-23390 and lorcaserin significantly reduced nicotine self-administration when given alone and had additive effects when given in combination. In the chronic study, each drug alone caused a significant decrease in nicotine self-administration. No additive effect was seen in combination because SCH-23390 given alone chronically was already highly effective. Chronic administration of the combination was not seen to significantly prolong reduced nicotine self-administration into the post-treatment period. This research shows that unlike lorcaserin and SCH-23390 interactions when given acutely, when given chronically in combination they do not potentiate or prolong each other's effects in reducing nicotine self-administration.