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Neuron. 2015 Dec 2;88(5):1054-1066. doi: 10.1016/j.neuron.2015.10.017. Epub 2015 Nov 12.

Sufficiency of Mesolimbic Dopamine Neuron Stimulation for the Progression to Addiction.

Author information

1
Department of Basic Neurosciences, Medical Faculty, University of Geneva, 1211 Geneva, Switzerland.
2
Department of Basic Neurosciences, Medical Faculty, University of Geneva, 1211 Geneva, Switzerland; Clinic of Neurology, Department of Clinical Neurosciences, Geneva University Hospital, 1211 Geneva, Switzerland. Electronic address: christian.luscher@unige.ch.

Abstract

The factors causing the transition from recreational drug consumption to addiction remain largely unknown. It has not been tested whether dopamine (DA) is sufficient to trigger this process. Here we use optogenetic self-stimulation of DA neurons of the ventral tegmental area (VTA) to selectively mimic the defining commonality of addictive drugs. All mice readily acquired self-stimulation. After weeks of abstinence, cue-induced relapse was observed in parallel with a potentiation of excitatory afferents onto D1 receptor-expressing neurons of the nucleus accumbens (NAc). When the mice had to endure a mild electric foot shock to obtain a stimulation, some stopped while others persevered. The resistance to punishment was associated with enhanced neural activity in the orbitofrontal cortex (OFC) while chemogenetic inhibition of the OFC reduced compulsivity. Together, these results show that stimulating VTA DA neurons induces behavioral and cellular hallmarks of addiction, indicating sufficiency for the induction and progression of the disease.

PMID:
26586182
DOI:
10.1016/j.neuron.2015.10.017
[Indexed for MEDLINE]
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