RT Journal Article
SR Electronic
T1 Cocaine-Induced Reinstatement Requires Endogenous Stimulation of μ-Opioid Receptors in the Ventral Pallidum
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 4512
OP 4520
DO 10.1523/JNEUROSCI.0685-05.2005
VO 25
IS 18
A1 Tang, Xing-Chun
A1 McFarland, Krista
A1 Cagle, Stephanie
A1 Kalivas, Peter W.
YR 2005
UL http://www.jneurosci.org/content/25/18/4512.abstract
AB The projection from the nucleus accumbens to the ventral pallidum regulates the reinstatement of cocaine seeking in rats extinguished from cocaine self-administration. This projection coexpresses GABA and enkephalin, posing a role for μ-opioid receptors in the ventral pallidum in mediating the reinstatement of cocaine seeking. Rats were extinguished from cocaine self-administration, and the reinstatement of active lever pressing by cocaine was blocked by intra-ventral pallidum administration of the μ receptor antagonist Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) (0.03-3.0 μg). Conversely, stimulating μ receptors with morphine (1-30 μg) in the ventral pallidum reinstated cocaine seeking. The ability of intra-ventral pallidum morphine to reinstate lever pressing was blocked by co-microinjection of the μ antagonist CTAP and was augmented by systemic cocaine administration. The reinstatement of cocaine seeking was associated with reduced extracellular GABA in the ventral pallidum, and the reduction in GABA was also prevented by blocking μ receptors with CTAP (10 μm). Although immunoblotting revealed that neither the total tissue concentration nor the membrane insertion of μ receptors in the ventral pallidum was altered by withdrawal from cocaine, the capacity of morphine (0.01-10 μm) to reduce ventral pallidum levels of extracellular GABA was augmented in rats extinguished from cocaine self-administration. These data are consistent with the reinstatement of cocaine seeking being modulated in part by coreleased enkephalin and GABA from the accumbens-ventral pallidal projection, a modulation that may involve the inhibition of GABA release by presynaptic μ receptors.