Orphanin FQ/nociceptin blocks cocaine-induced behavioral sensitization in rats.
Psychopharmacology (Berl)
; 164(2): 168-76, 2002 Nov.
Article
em En
| MEDLINE
| ID: mdl-12404079
ABSTRACT
RATIONALE Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand of the opioid receptor-like (ORL-1) receptor, shows similarities to dynorphin A (1-17) in structure and functions. Dynorphin and other kappa opioid receptor agonists have been shown to block cocaine sensitization. OBJECTIVE:
The present study was designed to examine the ability of OFQ/N to block cocaine-induced behavioral sensitization.METHODS:
Rats were habituated to testing chambers for 1 h, injected with artificial cerebrospinal fluid (aCSF) or OFQ/N (15 nmol) followed by saline or cocaine (20 mg/kg) and locomotor activity was measured for a further 1 h. Rats were treated similarly for the next 2 days except the dose of OFQ/N was doubled on each subsequent day. Rats were then challenged with cocaine (7.5 mg/kg) in the absence of OFQ/N on day 8. The specificity of OFQ/N's action was examined in the presence of J-113397 (30 nmol), an ORL-1 receptor antagonist. The ability of OFQ/N to block the context-independent component of cocaine sensitization was also tested wherein rats were treated in their home cages on days 1-3. Finally, the effect of intra-VTA OFQ/N administration on cocaine sensitization was examined.RESULTS:
Sensitization did not develop in rats repeatedly treated with OFQ/N, via either route of administration, prior to cocaine administration on days 1-3. The inhibitory effect of OFQ/N was not dependent on context and was blocked by pretreatment with J-113397.CONCLUSION:
Our results indicate that OFQ/N blocks cocaine-induced behavioral sensitization through activation of the ORL-1 receptor and that the VTA may be one of the substrates for this action of OFQ/N.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cocaína
/
Peptídeos Opioides
/
Locomoção
Limite:
Animals
Idioma:
En
Revista:
Psychopharmacology (Berl)
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Estados Unidos