CRF enhancement of GIRK channel-mediated transmission in dopamine neurons.
Dopamine neurons in the ventral midbrain contribute to learning and memory of natural and drug-related rewards. Corticotropin-releasing factor (CRF), a stress-related peptide, is thought to be involved in aspects of relapse following drug withdrawal, but the cellular actions are poorly understood. This study investigates the action of CRF on G-protein-linked inhibitory postsynaptic currents (IPSCs) mediated by GIRK (Kir3) channels in dopamine neurons. CRF enhanced the amplitude and slowed the kinetics of IPSCs following activation of D2-dopamine and GABA(B) receptors. This action was postsynaptic and dependent on the CRF(1) receptor. The enhancement induced by CRF was attenuated by repeated in vivo exposures to psychostimulants or restraint stress. The results indicate that CRF influences dopamine- and GABA-mediated inhibition in the midbrain, suggesting implications for the chronic actions of psychostimulants and stress on dopamine-mediated behaviors.
Beckstead
Michael J
MJ
Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA.
Gantz
Stephanie C
SC
Ford
Christopher P
CP
Stenzel-Poore
Mary P
MP
Phillips
Paul Em
PE
Mark
Gregory P
GP
Williams
John T
JT
D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism; D012008:Recurrence; D012054:Reinforcement, Psychology; D012149:Restraint, Physical / Q000502:physiology / Q000523:psychology; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000503:physiopathology; D019966:Substance-Related Disorders / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism; D000099052:CRF Receptor, Type 1
D000697:Central Nervous System Stimulants; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018019:Receptors, Corticotropin-Releasing Hormone; D017448:Receptors, Dopamine D2; D018080:Receptors, GABA-B; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone