D1 dopamine receptor-mediated LTP at GABA synapses encodes motivation to self-administer cocaine in rats.
Journal of Neuroscience. 2013-07-17; 33(29): 11960-11971
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1. J Neurosci. 2013 Jul 17;33(29):11960-71. doi: 10.1523/JNEUROSCI.1784-13.2013.
D1 dopamine receptor-mediated LTP at GABA synapses encodes motivation to
self-administer cocaine in rats.
Krawczyk M(1), Mason X, DeBacker J, Sharma R, Normandeau CP, Hawken ER, Di
Prospero C, Chiang C, Martinez A, Jones AA, Doudnikoff É, Caille S, Bézard E,
Georges F, Dumont ÉC.
(1)Department of Biomedical and Molecular Sciences and Center for Neuroscience
Studies, Queen’s University, Kingston, Ontario K7L 3N6, Canada.
Enhanced motivation to take drugs is a central characteristic of addiction, yet
the neural underpinning of this maladaptive behavior is still largely unknown.
Here, we report a D1-like dopamine receptor (DRD1)-mediated long-term
potentiation of GABAA-IPSCs (D1-LTPGABA) in the oval bed nucleus of the stria
terminalis that was positively correlated with motivation to self-administer
cocaine in rats. Likewise, in vivo intra-oval bed nucleus of the stria terminalis
DRD1 pharmacological blockade reduced lever pressing for cocaine more effectively
in rats showing enhanced motivation toward cocaine. D1-LTPGABA resulted from
enhanced function and expression of G-protein-independent DRD1 coupled to c-Src
tyrosine kinases and required local release of neurotensin. There was no
D1-LTPGABA in rats that self-administered sucrose, in those with limited cocaine
self-administration experience, or in those that received cocaine passively
(yoked). Therefore, our study reveals a novel neurophysiological mechanism
contributing to individual motivation to self-administer cocaine, a critical
psychobiological element of compulsive drug use and addiction.
PMID: 23864683 [Indexed for MEDLINE]