PubMed · 16326320
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Victoria Hekkers. Will mediation help?. https://doi.org/10.1016/j.casemgr.2005.08.009
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Numerous studies indicate that gamma-hydroxybutyric acid (GHB) influences the endogenous dopamine system. Both GHB and most dopaminergic D(2) receptor antagonists are effective anti-aggressive agents in animal models. The present study aimed to investigate the effects of GHB on agonistic behaviour and to implicate D(2) dopamine receptor on these behaviours. For this purpose, the effects of GHB (80, 120 and 160 mg/kg, IP) and tiapride (60 mg/kg) administered alone or in combination were examined on agonistic behaviour elicited by 'isolation' in male mice. Individually housed mice were exposed to anosmic "standard opponents" 30 min after drug administration, and the encounters were videotaped and evaluated using an ethologically based analysis. The administration of 80 and 120 mg/kg of GHB reduced threat without impairing motor activity, but the administration of 160 mg/kg of GHB or the co-administration of GHB+tiapride (a selective D(2) receptor antagonist) significantly reduced threat and attack but concomitantly increased immobility. The co-administration of GHB+tiapride had different effects to those observed by the administration of these drugs separately. It is concluded that the anti-aggressive effect of GHB appears to be mediated, at least in part, by D(2) dopamine receptors. This anti-dopaminergic activity is an indirect effect, probably induced by the activation of GHB receptors of low affinity, and in this way, this compound would reduce levels of dopamine without blockading of D(2) postsynaptic dopamine receptors.
We tested the ability of 3,4-methylenedioxymethamphetamine (MDMA) to induce conditioned place preference (CPP) in dominant and subordinate OF-1 mice subjected to cohabitation and repeated sessions of agonistic confrontation, as well as in non-confronted mice. We selected doses of MDMA (2, 6, 10 mg/kg) previously reported to induce CPP in mice and we measured expression of c-Fos evoked by the treatments in non-confronted mice. MDMA induced c-Fos protein in several corticolimbic regions involved in drug-induced reward. Mice were exposed to brief sessions of agonistic confrontation on 5 consecutive days. Determinations of circulating hormones and drug conditioning tests were carried out on completion of the encounters. The results of hormone assays indicated that dominant mice had higher serum concentrations of testosterone, but lower levels of corticosterone, than submissive mice. Post-conditioning tests after drug conditioning (4 injections of MDMA or saline on alternate days) showed that MDMA significantly produced CPP at doses of 2 and 6 mg/kg, but not at 10 mg/kg, an inverted U-shaped pattern of conditioning that was invariable in non-confronted, dominant and subordinate mice. These results demonstrate that the endocrine and behavioural correlates linked to social status and social stress in mice are not paralleled by significant changes in the rewarding efficacy of MDMA in the CPP paradigm under the specific conditions tested.
Operant procedures combined with pharmacological manipulations have implicated a role for the dopaminergic system in the perception and production of temporal intervals. Because studies have suggested that animals use temporal information to organize food protection behavior, the current study investigates whether dopaminergic systems are involved in timing during this natural behavior. The experiment examined the influence of a dopaminergic agonist (amphetamine) and an antagonist (haloperidol) on food protection behavior initiated to avoid theft by a conspecific. Amphetamine increased the time spent dodging and decreased the time spent bracing during the consumption of a hazelnut. On the other hand, haloperidol decreased the time spent dodging while showing no systematic changes in bracing. Topographic and kinematic analyses of rat movement conflicted with motivational, motoric, and social accounts of drug-induced changes in food protection behavior organization. These observations provide evidence that rats use temporal information to organize movements in the natural behavior of protecting food from theft by a conspecific, and this organization is influenced by both a dopaminergic agonist and an antagonist.