title: Simultaneous dopamine and single-unit recordings reveal accumbens GABAergic responses: implications for intracranial self-stimulation.
abstract: Intracranial self-stimulation (ICS) is a motivated behavior that results from contingent activation of the brain reward system. ICS with stimulating electrodes placed in the medial forebrain bundle (MFB) is particularly robust. However, the neurons that course through this pathway use a variety of neurotransmitters including dopamine and GABA. For this reason, the neurotransmitters that are central to this behavior, and the specific roles that they subserve, remain unclear. Here, we used extracellular electrophysiology and cyclic voltammetry at the same electrode in awake rats to simultaneously examine cell firing and dopamine release in the nucleus accumbens (NAc) during ICS and noncontingent stimulation of the MFB. ICS elicited dopamine release in the NAc and produced coincident time-locked changes (predominantly inhibitions) in the activity of a subset of NAc neurons. Similar responses were elicited with noncontingent stimulations. The changes in firing rate induced by noncontingent stimulations were reversed by the GABA(A) receptor antagonist bicuculline. Most time-locked unit activity was unaffected by D1 or D2-like dopamine-receptor antagonists, or by inhibition of evoked dopamine release, although, for a minority of units, the D1 dopamine-receptor antagonist SCH23390 attenuated neural activity. Thus, neurons in the NAc are preferentially inhibited by GABA(A) receptors after MFB stimulation, a mechanism that may also be important in ICS.
authors.affiliation: Department of Chemistry and Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Cheer
authors.forename: Michael L A V
authors.initials: ML
authors.lastname: Heien
authors.forename: Paul A
authors.initials: PA
authors.lastname: Garris
authors.forename: Regina M
authors.initials: RM
authors.lastname: Carelli
authors.forename: R Mark
authors.initials: RM
authors.lastname: Wightman
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004566:Electrodes; D004594:Electrophysiology; D005071:Evoked Potentials; D018757:GABA Modulators / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D013997:Time Factors
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D018757:GABA Modulators; D018377:Neurotransmitter Agents; D017447:Receptors, Dopamine D1; D004298:Dopamine; D001640:Bicuculline