Illicit use of gamma-Hydroxy butyrate (GHB), a popular new """"""""club drug,"""""""" has reached mini-epidemic levels in America. GHB is also in clinical trials for treatment of narcolepsy and alcohol addiction. GHB is pharmacologically unique among drugs of abuse because it is a naturally occurring substance in mammalian brain with its own receptor(s) and uptake system. Although reports of GHB abuse are rising rapidly, information about the interactions of GHB with the central dopamine systems that mediate drug reward and craving is conflicting. The purpose of the present proposal is to determine the effect of GHB on extracellular dopamine concentrations in awake rats using fast scan cyclic voltammetry. We will: (1) Determine dose- response relationships for the effects of GHB on electrically-stimulated dopamine concentrations in the caudate and the shell of the nucleus accumbens and resolve its effects on dopamine release and uptake kinetics, (2) Determine if repeated GHB exposure modifies the regulatory mechanisms that govern extracellular dopamine concentrations and alters the acute response to GHB. This research will study five doses of GHB that reflect human doses ranging from therapeutics to abuse. I hypothesize that low doses of GHB will increase dopamine release slightly in the caudate and nucleus accumbens and that high doses will robustly elevate dopamine release in both regions. These studies will utilize gastric administration of GHB in awake rats to provide realistic information about GHB effects on central dopamine neurotransmission
