Kappa opioid receptors regulate stress-induced cocaine seeking and synaptic plasticity

Nicholas M. Graziane, Abigail M. Polter, Lisa A. Briand, R. Christopher Pierce, Julie A. Kauer

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Stress facilitates reinstatement of addictive drug seeking in animals and promotes relapse in humans. Acute stress has marked and long-lasting effects on plasticity at both inhibitory and excitatory synapses on dopamine neurons in the ventral tegmental area (VTA), a key region necessary for drug reinforcement. Stress blocks long-term potentiation at GABAergic synapses on dopamine neurons in the VTA (LTPGABA), potentially removing a normal brake on activity. Here we show that blocking kappa opioid receptors (KORs) prior to forced-swim stress rescues LTPGABA. In contrast, blocking KORs does not prevent stress-induced potentiation of excitatory synapses nor morphine-induced block of LTPGABA. Using a kappa receptor antagonist as a selective tool to test the role of LTPGABA in vivo, we find that blocking KORs within the VTA prior to forced-swim stress prevents reinstatement of cocaine seeking. These results suggest that KORs may represent a useful therapeutic target for treatment of stresstriggered relapse in substance abuse.

Original languageEnglish (US)
Pages (from-to)942-954
Number of pages13
JournalNeuron
Volume77
Issue number5
DOIs
StatePublished - 2013

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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