Comparison of intra-accumbens injection of histamine with histamine H1-receptor antagonist chlorpheniramine in effects on reinforcement and memory parameters

Histaminergic neurons are located exclusively in the tuberomammillary nucle i (TM) of the hypothalamus from where they project to many regions of the b rain including the basal ganglia. Earlier experiments led to the hypothesis that neuronal histamine (HA), particularly in relation to the HI receptor, has an inhibitory role in learning and reward-related processes. Based on this premise, the objective of the present study was to compare HA with the H1-receptor antagonist d-chlorpheniramine (CPR) in effects on reinforcemen t and memory parameters after injection into different subregions of the ra t nucleus accumbens (NAcc). In the first experiment, mnemoactive effects of CPR (0.1 - 10 mug) were assessed after injection into the caudal or rostra l part of the NAcc with the one-trial uphill avoidance task as a measure of learning. The data show that intra-NAcc injection of CPR (10 mug) facilita ted retention of the task, when the compound was administered immediately a fter training. This effect was evident only when CPR was administered into the caudal-shell but not into the rostral pole of the NAcc providing eviden ce for anatomical specificity of the intra-NAcc induced promotion of memory . In the second experiment, possible mnemonic and reinforcing effects of HA (0.001-1 mug) were gauged after injection of the amine into the caudal NAc c, using post-trial application in the uphill avoidance task to assess effe cts on learning and place preference as an index of reinforcing properties. The data show that caudal-NAcc injection of HA (0.1 mug) improved retentio n of the avoidance task and produced place preference indicative of a reinf orcing action. The finding that intra-NAcc injection of HA can facilitate l earning and has reinforcing effects is at variance with the proposed inhibi tory nature of neuronal HA in reward-related processes. Thus, the disinhibi tion of reinforcement and facilitation of learning found earlier after part ial destruction of TM-intrinsic neurons might not necessarily be related to a lesion-induced reduction of the HAergic tone. The observation that CPR h as behavioral effects quite similar to HA suggests that the mnemoactive and reinforcing action of this compound might involve pharmacodynamic aspects beyond its antagonistic activity at H1-receptive sites. (C) 2001 Elsevier S cience BN. All rights reserved.