Dopaminergic effects of histamine administration in the nucleus accumbens and the impact of H1-receptor blockade

The mesolimbic dopamine system is thought to play a critical role in reward -related processes. A number of studies have shown that lesion or inhibitio n of histaminergic neurons acting through H1 receptors can potentiate the e ffects of drug-induced reward (e.g., psychostimulants and opioids) and can enhance the reinforcing effects of electrical stimulation of the brain. Sin ce dopamine transmission in the nucleus accumbens is thought to provide a c rucial link in these histaminergic actions, we examined the effects of loca l histamine application (0.1, 1.0 and 10.0 mu mol/l) on dopamine and its me tabolites in the nucleus accumbens of anesthetized rats by means of unilate ral reverse dialysis. To study the influence of H1 receptors, we also appli ed the Hi-receptor antagonist pyrilamine (10.0 and 20.0 mg/kg, intraperiton eally) 20 min before histamine administration (1 mmol/l). Finally, pyrilami ne (0.1, 1.0 and 10.0 mu mol/l) was locally administered into the nucleus a ccumbens. The data show that histamine can enhance extracellular dopamine l evels in the nucleus accumbens in a dose-dependent way. This increase was p artially antagonized by prior peripheral administration of 10 mg/kg, and wa s completely blocked by 20 mg/kg, of pyrilamine. Finally, intra-accumbens a dministration of pyrilamine locally decreased dopamine and increased dihydr oxyphenylacetic acid and homovanillic acid levels. These data are discussed with respect to the possible interactions between dopaminergic and histami nergic mechanisms in the mesolimbic system and their relation to mechanisms of reinforcement. (C) 2001 Elsevier Science Ltd. All rights reserved.