Aims: The present study investigated the effect of the gamma-aminobutyric acid (GABA)(B) receptor agonists, baclofen and CGP 44532, on the acquisition of alcohol drinking behaviour in selectively bred Sardinian alcohol-preferring (sP) rats.
Methods: Baclofen [0, 1 and 3 mg/kg, intraperitoneally (i.p.)] and CGP 44532 (0, 0.1, 0.3 and 1 mg/kg, i.p.) were administered immediately before alcohol presentation to alcohol-naive sP rats. Alcohol was offered under the two-bottle free-choice regimen with unlimited access for 24 h/day. Drug treatment was repeated once daily for 10 consecutive days.
Results: Baclofen and CGP 44532, dose-dependently and with comparable efficacy, suppressed alcohol intake; compensatory increases in water intake left total fluid intakes virtually unchanged.
Conclusions: These results demonstrate that baclofen and CGP 44532 prevent the acquisition of alcohol drinking behaviour in sP rats, and suggest the involvement of the GABA(B) receptor in the mechanisms underlying the disclosure and experience of the reinforcing properties of alcohol in this rat line.
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http://dx.doi.org/10.1093/alcalc/37.5.499 | DOI Listing |
Neuropharmacology
October 2015
Department of Psychiatry, Health Sciences, University of California San Diego, La Jolla, CA, USA; Veterans Affairs Center of Excellence for Stress and Mental Health, La Jolla, CA, USA. Electronic address:
GABAB (γ-aminobutyric acid B) receptors may be a therapeutic target for anxiety disorders. Here we characterized the effects of the GABAB receptor positive allosteric modulator (PAM) BHF177 on conditioned and unconditioned physiological responses to threat in the light-enhanced startle (LES), stress-induced hyperthermia, and fear-potentiated startle (FPS) procedures in rats. The effects of BHF177 on LES were compared with those of the GABAB receptor agonists baclofen and CGP44532, and the positive control buspirone, a 5-HT1A receptor partial agonist with anxiolytic activity in humans.
View Article and Find Full Text PDFBr J Pharmacol
July 2011
Department of Neurobiology, Institute of Pharmacology PAS, 31-343 Kraków, Poland.
Background And Purpose: An important role of GABAergic neurotransmission in schizophrenia was proposed a long time ago, but there is limited data to support this hypothesis. In the present study we decided to investigate GABA(B) receptor ligands in animal models predictive for the antipsychotic activity of drugs. The GABA(B) receptor antagonists CGP51176 and CGP36742, agonist CGP44532 and positive allosteric modulator GS39783 were studied.
View Article and Find Full Text PDFEur J Pharmacol
March 2011
Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA 92093-0603, USA.
Nicotine dependence is maintained by the aversive, depression-like effects of nicotine withdrawal and the rewarding effects of acute nicotine. GABA(B) receptor antagonists exhibit antidepressant-like effects in rodents, whereas GABA(B) receptor agonists attenuate the rewarding effects of nicotine. Recent studies with GABA(B) receptor positive modulators showed that these compounds represent potentially improved medications for the treatment of nicotine dependence because of fewer side-effects than GABA(B) receptor agonists.
View Article and Find Full Text PDFPharmacol Rep
September 2008
Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland.
GABAergic hypothesis of anxiety was introduced many years ago, however, a limited number of supporting data were accumulated so far and the role of GABA(B) receptors in behavioral processes related to the anxiety disorders has not been resolved. In the present study, we examined anxiolytic activity of CGP 36742, a potent and selective GABA(B) receptor antagonist, in rodent tests/models. We have demonstrated that CGP 36742 (30 mg/kg) is active in several animal tests detecting anxiolytic activity (the elevated plus-maze, conflict drinking test and four-plate test).
View Article and Find Full Text PDFBioorg Med Chem Lett
January 2008
The Adrien Albert Laboratory of Medicinal Chemistry, Department of Pharmacology, The University of Sydney, NSW 2006, Australia.
The R- and S-enantiomers of 4-amino-3-hydroxybutanoic acid (GABOB) were full agonists at human recombinant rho1 GABA(C) receptors. Their enantioselectivity (R>S) matched that reported for their agonist actions at GABA(B) receptors, but was the opposite to that reported at GABA(A) receptors (S>R). The corresponding methylphosphinic acid analogues proved to be rho1 GABA(C) receptor antagonists with R(+)-CGP44533 being more potent than S(-)-CGP44532, thus showing the opposite enantioselectivity to the agonists R(-)- and S(+)-GABOB.
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