title: Kappa opioid receptors regulate stress-induced cocaine seeking and synaptic plasticity.
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 stress-triggered relapse in substance abuse.
authors.affiliation: Brown University, Department of Molecular Pharmacology, Physiology and Biotechnology, Providence, RI 02912, USA.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Graziane
authors.forename: Abigail M
authors.initials: AM
authors.lastname: Polter
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Briand
authors.forename: R Christopher
authors.initials: RC
authors.lastname: Pierce
authors.forename: Julie A
authors.initials: JA
authors.lastname: Kauer
mesh_terms: D000818:Animals; D019970:Cocaine-Related Disorders / Q000503:physiopathology / Q000523:psychology*; D059290:Dopaminergic Neurons / Q000502:physiology; D058999:Drug-Seeking Behavior / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation; D008845:Microinjections; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000502:physiology; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000502:physiology*; D012008:Recurrence; D012646:Self Administration; D013315:Stress, Psychological / Q000503:physiopathology / Q000523:psychology*; D013550:Swimming / Q000523:psychology; D013569:Synapses / Q000502:physiology; D017557:Ventral Tegmental Area / Q000502:physiology
chemical_list: D018079:Receptors, GABA; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone