title: CRF antagonism within the ventral tegmental area but not the extended amygdala attenuates the anxiogenic effects of cocaine in rats.
abstract: In addition to its initial rewarding effects, cocaine has been shown to produce profound negative/anxiogenic actions. Recent work on the anxiogenic effects of cocaine has examined the role of corticotropin releasing factor (CRF), with particular attention paid to the CRF cell bodies resident to the extended amygdala (i.e., the central nucleus of the amygdala [CeA] and the bed nucleus of the stria terminalis [BNST]) and the interconnections within and projections outside the region (e.g., to the ventral tegmental area [VTA]). In the current study, localized CRF receptor antagonism was produced by intra-BNST, intra-CeA or intra-VTA application of the CRF antagonists, D-Phe CRF(12-41) or astressin-B. The effect of these treatments were examined in a runway model of i.v. cocaine self-administration that has been shown to be sensitive to both the initial rewarding and delayed anxiogenic effects of the drug in the same animal on the same trial. These dual actions of cocaine are reflected in the development of an approach-avoidance conflict ("retreat behaviors") about goal box entry that stems from the mixed associations that subjects form about the goal. CRF antagonism within the VTA, but not the CeA or BNST, significantly reduced the frequency of approach-avoidance retreat behaviors while leaving start latencies (an index of the positive incentive properties of cocaine) unaffected. These results suggest that the critical CRF receptors contributing to the anxiogenic state associated with acute cocaine administration may lie outside the extended amygdala, and likely involve CRF projections to the VTA.
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychological & Brain Sciences, University of California, Santa Barbara, CA 93106-9660, United States. Electronic address: aaron.ettenberg@psych.ucsb.edu.
authors.forename: Aaron
authors.initials: A
authors.lastname: Ettenberg
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychological & Brain Sciences, University of California, Santa Barbara, CA 93106-9660, United States.
authors.forename: Samuel W
authors.initials: SW
authors.lastname: Cotten
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychological & Brain Sciences, University of California, Santa Barbara, CA 93106-9660, United States.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Brito
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychological & Brain Sciences, University of California, Santa Barbara, CA 93106-9660, United States.
authors.forename: Adam K
authors.initials: AK
authors.lastname: Klein
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychological & Brain Sciences, University of California, Santa Barbara, CA 93106-9660, United States.
authors.forename: Tatum A
authors.initials: TA
authors.lastname: Ohana
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychological & Brain Sciences, University of California, Santa Barbara, CA 93106-9660, United States.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Margolin
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychological & Brain Sciences, University of California, Santa Barbara, CA 93106-9660, United States.
authors.forename: Alex
authors.initials: A
authors.lastname: Wei
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychological & Brain Sciences, University of California, Santa Barbara, CA 93106-9660, United States.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Wenzel
mesh_terms: D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000517:prevention & control*; D003042:Cocaine; D003346:Corticotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D012686:Septal Nuclei / Q000187:drug effects; D017557:Ventral Tegmental Area / Q000187:drug effects*
chemical_list: D010446:Peptide Fragments; C120841:astressin B; C113202:phenylalanyl corticotropin-releasing factor (12-41); D003346:Corticotropin-Releasing Hormone; D003042:Cocaine
keywords: Anxiety; Cocaine; Corticotropin-releasing factor; Drug self-administration; Extended amygdala; Operant runway