D1 dopamine receptor-mediated LTP at GABA synapses encodes motivation to self-administer cocaine in rats.

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Krawczyk, Michal | Mason, Xenos | Debacker, Julian | Sharma, Robyn | Normandeau, Catherine P | Hawken, Emily R | Di Prospero, Cynthia | Chiang, Cindy | Martinez, Audrey | Jones, Andrea A | Doudnikoff, Évelyne | Caille, Stephanie | Bézard, Erwan | Georges, François | Dumont, Éric C

Edité par CCSD ; Society for Neuroscience -

International audience. 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.

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