| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 3057330 | Experimental Neurology | 2006 | 13 Pages |
Opiate activation of mu-opioid receptors (μORs) in the ventral tegmental area (VTA) modulates γ-aminobutyric acid (GABA) neurotransmission within the mesocorticolimbic dopamine (DA) reward system. We combined in vivo extracellular electrophysiological recordings in anesthetized and freely behaving rats with intracellular Neurobiotin™ filling and immunocytochemistry to characterize the effects of opiates on VTA GABA neurons, evaluate their discharge activity during opiate self-administration, and identify the cellular sites for opiate activation. We identified a subpopulation of VTA GABA neurons that was characterized by location, spike discharge profile, activation by microelectrophoretic DA, and response to internal capsule (IC) stimulation. Systemic administration of heroin or microelectrophoretic application of the selective μOR agonist [d-Ala2, N-Me-Phe4, Gly-ol]-Enkephalin (DAMGO) reduced VTA GABA neuron firing rate (heroin IC50 = 0.35 mg/kg) and was blocked by the μOR antagonist naloxone. Heroin also reduced IC-evoked post-stimulus spike discharges, a manifestation of gap-junction-mediated electrical coupling between VTA GABA neurons. The baseline firing rate of VTA GABA neurons significantly increased (239%) following the acquisition of heroin self-administration behavior and transiently increased during each response for heroin (105%), but decreased (49%) following heroin, similar to non-contingent heroin. Electrophysiologically characterized VTA GABA neurons were filled with Neurobiotin™ and labeled dendrites contained plasmalemmal μOR immunoreactivity. Dually labeled μOR dendrites contained dendrodendritic appositions characteristic of gap junctions. These findings indicate that inhibition of this population of GABAergic neurons by opiates acting on dendritic μORs has implications for modulation of electrical coupling between VTA GABA neurons and dopamine (DA) neurotransmission in the VTA and terminal field regions.
