Comparison of intra-accumbens injection of histamine with histamine H1-receptor antagonist chlorpheniramine in effects on reinforcement and memory parameters
Ru. Hasenohrl et al., Comparison of intra-accumbens injection of histamine with histamine H1-receptor antagonist chlorpheniramine in effects on reinforcement and memory parameters, BEH BRA RES, 124(2), 2001, pp. 203-211
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.