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

Jill Watson, Sara Guzzetti, Carlotta Franchi, Angelo Di Clemente, Silvia Burbassi, Zsuzsa Emri, Nathalie Leresche, H. Rheinallt Parri, Vincenzo Crunelli, Luigi Cervo

Research output: Contribution to journalArticle

Abstract

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.
LanguageEnglish
Pages143-153
Number of pages11
JournalInternational Journal of Neuropsychopharmacology
Volume13
Issue number2
Early online date2 Sep 2009
DOIs
Publication statusPublished - Mar 2010

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Sodium Oxybate
Ventral Tegmental Area
Self Administration
Neurons
Dopaminergic Neurons
Nucleus Accumbens
4-hydroxybutyric acid
Street Drugs

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

Cite this

Watson, Jill ; Guzzetti, Sara ; Franchi, Carlotta ; Di Clemente, Angelo ; Burbassi, Silvia ; Emri, Zsuzsa ; Leresche, Nathalie ; Parri, H. Rheinallt ; Crunelli, Vincenzo ; Cervo, Luigi. / Gamma-hydroxybutyrate does not maintain self-administration but induces conditioned place preference when injected in the ventral tegmental area. In: International Journal of Neuropsychopharmacology. 2010 ; Vol. 13, No. 2. pp. 143-153.
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abstract = "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.",
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Gamma-hydroxybutyrate does not maintain self-administration but induces conditioned place preference when injected in the ventral tegmental area. / Watson, Jill; Guzzetti, Sara; Franchi, Carlotta; Di Clemente, Angelo; Burbassi, Silvia; Emri, Zsuzsa; Leresche, Nathalie; Parri, H. Rheinallt; Crunelli, Vincenzo; Cervo, Luigi.

In: International Journal of Neuropsychopharmacology, Vol. 13, No. 2, 03.2010, p. 143-153.

Research output: Contribution to journalArticle

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