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

• Published in: The international journal of neuropsychopharmacology Vol. 13; no. 2; pp. 143 - 153
• Main Authors: Watson, Jill, Guzzetti, Sara, Franchi, Carlotta, Di Clemente, Angelo, Burbassi, Silvia, Emri, Zsuzsa, Leresche, Nathalie, Parri, H. Rheinallt, Crunelli, Vincenzo, Cervo, Luigi
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.03.2010; Oxford University Press; Oxford University Press (OUP)
• Subjects: Administration, Oral; Animals; Cognitive science; Conditioning, Operant - drug effects; Dose-Response Relationship, Drug; Injections, Intravenous; Male; Microinjections; Neuroscience; Nucleus Accumbens - drug effects; Rats; Rats, Wistar; Self Administration; Sodium Oxybate - administration & dosage; Sodium Oxybate - pharmacology; Ventral Tegmental Area - drug effects; GHB; nucleus accumbens; Conditioned place preference; ventral tegmental area; self-administration
• ISSN: 1461-1457; 1469-5111
• DOI: 10.1017/S1461145709990186

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 μg/0.5 μl 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 μg/0.5 μl 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.