title: Morphine history sensitizes postsynaptic GABA receptors on dorsal raphe serotonin neurons in a stress-induced relapse model in rats.
abstract: The serotonin (5-hydroxytryptamine, 5-HT) system plays an important role in stress-related psychiatric disorders and substance abuse. Previous work has shown that the dorsal raphe nucleus (DR)-5-HT system is inhibited by swim stress via stimulation of GABA synaptic activity by the stress neurohormone corticotropin-releasing factor (CRF). Additionally, the DR 5-HT system is regulated by opioids. The present study tests the hypothesis that the DR 5-HT system regulates stress-induced opioid relapse. In the first experiment, electrophysiological recordings of GABA synaptic activity in 5-HT DR neurons were conducted in brain slices from Sprague-Dawley rats that were exposed to swim stress-induced reinstatement of previously extinguished morphine conditioned place preference (CPP). Behavioral data indicate that swim stress triggers reinstatement of morphine CPP. Electrophysiology data indicate that 5-HT neurons in the morphine-conditioned group exposed to stress had increased amplitude of inhibitory postsynaptic currents (IPSCs), which would indicate greater postsynaptic GABA receptor density and/or sensitivity, compared to saline controls exposed to stress. In the second experiment, rats were exposed to either morphine or saline CPP and extinction, and then 5-HT DR neurons from both groups were examined for sensitivity to CRF in vitro. CRF induced a greater inward current in 5-HT neurons from morphine-conditioned subjects compared to saline-conditioned subjects. These data indicate that morphine history sensitizes 5-HT DR neurons to the GABAergic inhibitory effects of stress as well as to some of the effects of CRF. These mechanisms may sensitize subjects with a morphine history to the dysphoric effects of stressors and ultimately confer an enhanced vulnerability to stress-induced opioid relapse.
authors: Department of Anatomy and Cell Biology and Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, 3500 N. Broad St., PA 19140, USA.
authors: D R
authors: DR
authors: Staub
authors: J W
authors: JW
authors: Lunden
authors: A M
authors: AM
authors: Cathel
authors: E L
authors: EL
authors: Dolben
authors: L G
authors: LG
authors: Kirby
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D003627:Data Interpretation, Statistical; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005108:Extinction, Psychological; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000378:metabolism* / Q000523:psychology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects*; D012008:Recurrence; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D013315:Stress, Psychological / Q000523:psychology*
chemical_list: D018079:Receptors, GABA; D012701:Serotonin; D009020:Morphine; D003346:Corticotropin-Releasing Hormone