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Titolo:
Enduring resistance to extinction of cocaine-seeking behavior induced by drug-related cues
Autore:
Weiss, F; Martin-Fardon, R; Ciccocioppo, R; Kerr, TM; Smith, DL; Ben-Shahar, O;
Indirizzi:
Scripps Res Inst, Dept Neuropharmacol, La Jolla, CA 92037 USA Scripps Res Inst La Jolla CA USA 92037 opharmacol, La Jolla, CA 92037 USA Univ Calif Santa Barbara, Dept Psychol, Santa Barbara, CA 93106 USA Univ Calif Santa Barbara Santa Barbara CA USA 93106 Barbara, CA 93106 USA
Titolo Testata:
NEUROPSYCHOPHARMACOLOGY
fascicolo: 3, volume: 25, anno: 2001,
pagine: 361 - 372
SICI:
0893-133X(200109)25:3<361:ERTEOC>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
EXTRACELLULAR DOPAMINE LEVELS; SELF-ADMINISTERED COCAINE; NUCLEUS-ACCUMBENS; ENVIRONMENTAL DETERMINANTS; DISCRIMINATIVE STIMULI; PROLONGED EXTINCTION; RECEPTOR AGONISTS; RHESUS-MONKEYS; RATS; RELAPSE;
Keywords:
reinstatement; relapse; dopamine; SCH 39166; SKF 81297; PD 128907; discriminative stimulus; conditioned stimulus; occasion setter;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Weiss, F Scripps Res Inst, Dept Neuropharmacol, CVN-15,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA Scripps Res Inst CVN-15,10550 N Torrey Pines Rd La Jolla CA USA 92037
Citazione:
F. Weiss et al., "Enduring resistance to extinction of cocaine-seeking behavior induced by drug-related cues", NEUROPSYCH, 25(3), 2001, pp. 361-372

Abstract

The conditioning of cocaine's pharmacological actions with environmental stimuli is thought to be a critical factor in long-lasting relapse risk associated with cocaine addiction. To study the significance of environmental stimuli in enduring vulnerability to relapse, the resistance to extinction of drug-seeking behavior elicited by a cocaine-related stimulus was examined. Male Wistar rats were trained to associate discriminative stimuli (S-D) with the availability of intravenous cocaine (S+) vs. the availability of non-rewarding (S-) saline solution, and then placed on extinction conditions during which intravenous solutions and S-D were withheld. The rats were then presented with the S+ or S- alone in 60-min reinstatement sessions conducted at 3-day intervals. To examine the long-term persistence of the motivating effects of the cocaine S+, a subgroup of rats was re-tested following an additional three months of abstinence during which time the rats remainedconfined to their home cages. Re-exposure to the cocaine S+ selectively elicited robust responding at the previously active lever. The efficacy and selectivity of this stimulus to elicit responding remained unaltered throughout a 34-day phase of repeated testing as well as following the additional extended abstinence period. In pharmacological tests, conducted in a separate group of rats, the dopamine (DA) D-1 antagonist SCH 39166 (10 mug/kg), the D-2/3 antagonist nafadotride (1 mg/kg), and the D-2/3 agonist PD 128907 (0.3 mg/kg) suppressed the cue-induced response reinstatement while the D-1agonist SKF 81297 (1.0 mg/kg) produced a variable behavioral profile attenuating cue-induced responding in some rats while exacerbating this behaviorin others. The results suggest that the motivating effects of cocaine-related stimuli are highly resistant to extinction. The undiminished efficacy of the cocaine S+ to induce drug-seeking behavior both with repeated testingand following long-term abstinence parallels the long-lasting nature of conditioned cue reactivity and cite-induced cocaine craving in humans, and confirms a significant role of learning factors in long-lasting vulnerabilityto relapse associated with cocaine addiction. Finally, the results supporta role of DA neurotransmission in cue-induced cocaine-seeking behavior. (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 22:30:28