PT  - JOURNAL ARTICLE
AU  - Michal Krawczyk
AU  - Xenos Mason
AU  - Julian DeBacker
AU  - Robyn Sharma
AU  - Catherine P. Normandeau
AU  - Emily R. Hawken
AU  - Cynthia Di Prospero
AU  - Cindy Chiang
AU  - Audrey Martinez
AU  - Andrea A. Jones
AU  - Évelyne Doudnikoff
AU  - Stephanie Caille
AU  - Erwan Bézard
AU  - François Georges
AU  - Éric C. Dumont
TI  - D1 Dopamine Receptor-Mediated LTP at GABA Synapses Encodes Motivation to Self-Administer Cocaine in Rats
AID  - 10.1523/JNEUROSCI.1784-13.2013
DP  - 2013 Jul 17
TA  - The Journal of Neuroscience
PG  - 11960--11971
VI  - 33
IP  - 29
4099  - http://www.jneurosci.org/content/33/29/11960.short
4100  - http://www.jneurosci.org/content/33/29/11960.full
SO  - J. Neurosci.2013 Jul 17; 33
AB  - 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.