The medial prefrontal cortex regulates the differential expression of morphine-conditioned place preference following a single exposure to controllable or uncontrollable stress.

Article date: 2008/3/28

PubMed ID: 1377716

Journal name: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (ISSN: 1740-634X)

DOI: 10.1038/npp.2008.34


Experiential factors, such as stress, are major determinants of vulnerability to drug addiction and relapse. The behavioral controllability of the stressor is a major determinant of how exposure to a stressor impacts addictive processes. Recent evidence suggests that controllable stressors, such as escapable shock (ES), activate ventral regions of the medial prefrontal cortex (mPFCv), whereas physically identical, but uncontrollable stress (inescapable shock, IS) does not. This activation is critical to the blunting effect that control has on neurochemical and behavioral sequelae of stress. Our laboratory has previously shown that IS, but not ES, potentiates morphine-conditioned place preference (CPP). However, the role of the mPFCv in this phenomenon is unknown. The present experiments investigated the role of the mPFCv during ES and IS in determining the effects of the stressor on subsequent morphine-CPP. Intra-mPFCv microinjection of the GABA(A) agonist muscimol 1 h before ES led ES to potentiate morphine-CPP, as does IS. Conversely, the potentiation of morphine-CPP normally observed in IS rats was blocked by intra-mPFCv microinjection of the GABA(A) antagonist picrotoxin 1 h before IS. These results suggest that during stress, activation of the mPFCv prevents subsequent potentiation of morphine-CPP, whereas inactivation of the mPFCv during stress does not. Thus, activation of the mPFCv during a stress experience is both necessary and sufficient to block the impact of stress on morphine-CPP, and control over stress blunts stress-induced potentiation of morphine effects by activating the mPFCv.

Author List: Rozeske Robert R, Der-Avakian Andre, Bland Sondra T, Beckley Jacob T, Watkins Linda R, Maier Steven F

Publication Types: Journal Article; Research Support, N.I.H., Extramural

Article Date: 2008/03/26

Substances mentioned in the article: GABA Agonists; GABA Antagonists; GABA-A Receptor Agonists; GABA-A Receptor Antagonists; Picrotoxin; Muscimol; Morphine;

Mesh terms: Analysis of Variance; Animals; Behavior, Animal/drug effects; Conditioning (Psychology); Escape Reaction/drug effects; GABA Agonists/pharmacology; GABA Antagonists/pharmacology; GABA-A Receptor Agonists; GABA-A Receptor Antagonists; Male; Microinjections; Morphine/pharmacology; Motor Activity/drug effects; Muscimol/pharmacology; Picrotoxin/pharmacology; Prefrontal Cortex/physiology; Rats; Rats, Sprague-Dawley; Stress, Psychological/physiopathology;

Citations: - 15338104

1377716.txt ยท Last modified: 2018/11/20 14:25 (external edit)