Gamma-hydroxybutyrate does not maintain self-administration but induces conditioned place preference when injected in the ventral tegmental area


Gamma-hydroxybutyric acid (GHB) is an endogenous brain substance that has diverse neuropharmacological actions, including rewarding properties in different animal species and in humans. As other drugs of abuse, GHB affects the firing of ventral tegmental neurons (VTA) in anaesthetized animals and hyperpolarizes dopaminergic neurons in VTA slices. However, no direct behavioural data on the effects of GHB applied in the VTA or in the target regions of its dopaminergic neurons, e.g. the nucleus accumbens (NAc), are available. Here, we investigated the effects of various doses of intravenous GHB in maintaining self-administration (from 0.001 to 10 mg/kg per infusion), and its ability to induce conditioned place preference (CPP) in rats when given orally (175-350 mg/kg) or injected directly either in the VTA or NAc (from 10 to 300 microg/0.5 microl per side). Our results indicate that while only 0.01 mg/kg per infusion GHB maintained self-administration, although not on every test day, 350 mg/kg GHB given orally induced CPP. CPP was also observed when GHB was injected in the VTA (30-100 microg/0.5 microl per side) but not in the NAc. Together with recent in-vitro findings, these results suggest that the rewarding properties of GHB mainly occur via disinhibition of VTA dopaminergic neurons.

Publication DOI:
Divisions: College of Health & Life Sciences > Clinical and Systems Neuroscience
College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
Uncontrolled Keywords: oral administration,animals,operant conditioning,drug dose-response relationship,intravenous injections,male,microinjections,nucleus accumbens,rats,Wistar rats,self administration,sodium oxybate,ventral tegmental area,Pharmacology (medical),Pharmacology,Psychiatry and Mental health
Publication ISSN: 1469-5111
Last Modified: 10 Jun 2024 07:09
Date Deposited: 11 Jul 2012 10:12
Full Text Link: http://journals ... ine&aid=7218100
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2010-03
Published Online Date: 2009-09-02
Authors: Watson, Jill
Guzzetti, Sara
Franchi, Carlotta
Di Clemente, Angelo
Burbassi, Silvia
Emri, Zsuzsa
Leresche, Nathalie
Parri, H. Rheinallt (ORCID Profile 0000-0002-1412-2688)
Crunelli, Vincenzo
Cervo, Luigi



Version: Published Version

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