Anti-aggressive effects of GHB in OF.1 strain mice: involvement of dopamine D2 receptors.
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.
Pedraza
Carmen
C
Department of Psychobiology, Faculty of Psychology, Campus de Teatinos, University of Málaga 29071 Málaga, Spain. mdpedraza@uma.es
Dávila
Guadalupe
G
Martín-López
Mercedes
M
Navarro
José Francisco
JF
D000378:Agonistic Behavior / Q000187:drug effects*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006885:Hydroxybutyrates / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D012919:Social Behavior; D012934:Social Isolation / Q000523:psychology; D013976:Tiapamil Hydrochloride / Q000494:pharmacology
D018492:Dopamine Antagonists; D004338:Drug Combinations; D006885:Hydroxybutyrates; D017448:Receptors, Dopamine D2; C111420:4-hydroxybutyric acid; D013976:Tiapamil Hydrochloride