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 nuclei (TM) of the hypothalamus from where they project to many regions of the brain including the basal ganglia. Earlier experiments led to the hypothesis that neuronal histamine (HA), particularly in relation to the H1 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 reinforcement and memory parameters after injection into different subregions of the rat nucleus accumbens (NAcc). In the first experiment, mnemoactive effects of CPR (0.1–10 μg) were assessed after injection into the caudal or rostral 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 μg) facilitated retention of the task, when the compound was administered immediately after training. This effect was evident only when CPR was administered into the caudal-shell but not into the rostral pole of the NAcc providing evidence 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 μg) were gauged after injection of the amine into the caudal NAcc, using post-trial application in the uphill avoidance task to assess effects on learning and place preference as an index of reinforcing properties. The data show that caudal-NAcc injection of HA (0.1 μg) improved retention of the avoidance task and produced place preference indicative of a reinforcing action. The finding that intra-NAcc injection of HA can facilitate learning and has reinforcing effects is at variance with the proposed inhibitory nature of neuronal HA in reward-related processes. Thus, the disinhibition of reinforcement and facilitation of learning found earlier after partial destruction of TM-intrinsic neurons might not necessarily be related to a lesion-induced reduction of the HAergic tone. The observation that CPR has 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.