Effects of Gamma-Hydroxybutyrate on Ventral Tegmental Unit Activity in the Rat: Considerations on REM Sleep Control
Hugo Tremblay 1, Roger Godbout 1,2,4, Véronique Girodias 1, Martine Schmitt 3 and Jean-Jacques Bourguignon 3
1Centre de biomédecine, Hôpital du Sacré-Coeur, Montréal, Québec, H4J 1C5, Canada 2Département de psychiatrie, Université de Montréal, Succ. Centre-Ville Montréal, Québec, H3C 3J7, Canada 3Laboratoire de Pharmacochimie moléculaire, Strasbourg Cedex, 67084, France
4Centre de recherche, Hôpital du Sacré-Coeur, Montréal, Québec, H4J 1C5, Canada
ABSTRACT
The effect of gamma-hydroxybutyrate (GHB) administration on spontaneously active dopaminergic cells of the ventral tegmental area (VTA) was determined using extracellular single unit recordings in urethane-anesthetized rats. High doses (160-250 mg/kg, i.p.) of GHB reversibly decreased firing rate in 63.6% of the cells tested (n=11); remaining cells (36.4%) were unaffected. When the GHB receptor antagonist NCS-382 (10 mg/kg, i.p.) was co-administered with GHB at high doses, 50% of the cells became excited while remaining cells were unaffected. Of the 34 cells tested with GHB at low doses (10 mg/kg, i.p.), 21 (61.8%) changed their firing activity. Of these, 12 (57.1%) were excited, five (23.8%) were inhibited, and four (19.0%) were first excited then totally inhibited (E/Ipattern). Out of the three E/I cells tested, two resumed their firing activity after apomorphine (50 µg/kg s.c.), showing that they were in a state of depolarization inactivation. When NCS-382 (10 mg/kg, i.p.) was co-administered with GHB at low doses, only two of the seven cells tested (28.6%) changed their firing activity, both with excitations. We conclude that only low doses of GHB selectively activate GHB receptors. Mechanisms by which low doses of GHB facilitate REM sleep are discussed.