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Titolo:
Different requirements for cAMP response element binding protein in positive and negative reinforcing properties of drugs of abuse
Autore:
Walters, CL; Blendy, JA;
Indirizzi:
Univ Penn, Dept Pharmacol, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 l & Behav, Philadelphia, PA 19104 USA
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 23, volume: 21, anno: 2001,
pagine: 9438 - 9444
SICI:
0270-6474(200112)21:23<9438:DRFCRE>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
CONDITIONED PLACE PREFERENCE; RAT LOCUS-COERULEUS; CHRONIC MORPHINE; OPIATE WITHDRAWAL; NUCLEUS-ACCUMBENS; MICE LACKING; DOPAMINE-TRANSPORTER; CREB PHOSPHORYLATION; TARGETED MUTATION; COCAINE REWARD;
Keywords:
mice; CREB; morphine; cocaine; conditioned place preference; sensitization;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Blendy, JA Univ Penn, Dept Pharmacol, Ctr Neurobiol & Behav, 125 John Morgan Bldg,3620 Hamilton Walk, Philadelphia, PA 19104 USA Univ Penn 125 John Morgan Bldg,3620 Hamilton Walk Philadelphia PA USA 19104
Citazione:
C.L. Walters e J.A. Blendy, "Different requirements for cAMP response element binding protein in positive and negative reinforcing properties of drugs of abuse", J NEUROSC, 21(23), 2001, pp. 9438-9444

Abstract

Addiction is a complex process that relies on the ability of an organism to integrate positive and negative properties of drugs of abuse. Therefore, studying the reinforcing as well as aversive components of drugs of abuse in a single model system will enable us to understand the role of final common mediators, such as cAMP response element-binding protein (CREB), in the addiction process. To this end, we analyzed mice with a mutation in the alpha and Delta isoforms of the CREB gene. Previously we have shown that CREBalpha Delta mutant mice in a mixed genetic background show attenuated signs of physical dependence, as measured by the classic signs of withdrawal. We have generated a uniform genetically stable F1 hybrid (129SvEv/C57BL/6) mouse line harboring the CREB mutation. We have found the functional activity of CREB in these F1 hybrid mice to be dramatically reduced compared with their wild-type littermates. These mice maintain a reduced withdrawal phenotype after chronic morphine. We are now poised to examine a number of complexbehavioral phenotypes related to addiction in a well defined CREB-deficient mouse model. We demonstrate that the aversive properties of morphine are still present in CREB mutant mice despite a reduction of physical withdrawal. On the other hand, these mice do not respond to the reinforcing properties of morphinein a conditioned place preference paradigm. In contrast, CREB mutant mice demonstrate an enhanced response to the reinforcing properties of cocaine compared with their wild-type controls in both conditioned place preference and sensitization behaviors. These data may provide the first paradigm for differential vulnerability to various drugs of abuse.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 20:24:53