Differential sensitivity of the caudal and rostral nucleus accumbens to the rewarding effects of a H1-histaminergic receptor blocker as measured withplace-preference and self-stimulation behavior

A recent series of studies in rats has demonstrated positively reinforcing and memory enhancing effects following lesions of the nucleus tuberomammill aris, which is the only known source of neuronal histamine. The aim of the present experiments was to assess whether inhibition of histaminergic neuro transmission in the ventral striatum has positively reinforcing effects. In Experiment 1 rats with chronically-implanted cannulae were injected with t he H1 receptor blocker d-(+)-chlorpheniramine at doses of 0.1, 1.0 and 10.0 mu g into the rostral or caudal parts of the nucleus accumbens, a brain re gion known to be involved in reward-related processes. Immediately after th e treatment the animals were placed into one of four restricted quadrants o f a circular open field (closed corral) for a single conditioning trial. Du ring the drug-free test for conditioned place preference, when a choice amo ng the four quadrants was provided, those rats injected with 10.0 mu g chlo rpheniramine in the caudal nucleus accumbens spent more time in the treatme nt corral, indicative of a positively rewarding drug action. In Experiment 2 the question was posed whether injection of chlorpheniramine into the nuc leus accumbens influences electrical self-stimulation of the lateral hypoth alamus. For this purpose rats were chronically implanted with two bipolar e lectrodes aimed at the lateral-hypothalami and with two additional guide ca nnulae aimed either at the rostral or caudal nucleus accumbens. After havin g established reliable self-stimulation behavior at one of the two electrod e sites the animals were allowed to self-stimulate for one hour (baseline). Then they were unilaterally injected with 10.0 mu g chlorpheniramine or ve hicle and allowed to self-stimulate for another hour (test). On the next da y the same procedure took place, except for the difference that the animals received an injection aimed at the hemisphere not treated so far. Animals treated with chlorpheniramine in the caudal and in the rostral nucleus accu mbens displayed higher rates of ipsihemispheric self-stimulation behavior. Moreover, the animals treated with the H1 receptor blocker in the caudal nu cleus accumbens displayed higher rates of ipsihemispheric self-stimulation than those having received an injection in the rostral pole. Upon completio n of this part of the experiment all animals received an additional intrape ritoneal treatment with chlorpheniramine (20 mg/kg) or vehicle, respectivel y, and were tested in the same way described above. This treatment also res ulted in an amplification of intracranial self-stimulation behavior. These results support the hypothesis that histaminergic neurotransmission i s involved in the inhibitory control of a central system subserving reward- related processes. The present data also further highlight the nucleus accu mbens as functionally heterogenous along its rostrocaudal axis, with the ca udal-shell subregion being more sensitive to antihistaminic induced reward than the rostral entity. (C) 1999 IBRO. Published by Elsevier Science Ltd.