Role of µ-opioid receptor reserve and µ-agonist efficacy as determinants of the effects of µ-agonists on intracranial self-stimulation in rats.
Behav Pharmacol
; 23(7): 678-92, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-22914074
ABSTRACT
The net effect of µ-opioid receptor agonists on intracranial self-stimulation (ICSS) in rats reflects an integration of rate-increasing and rate-decreasing effects. Previous opioid exposure is associated with tolerance to rate-decreasing effects and the augmented expression of abuse-related rate-increasing effects. This finding was replicated here with morphine. Subsequent studies then tested the hypothesis that opioid agonist-induced rate-decreasing effects require the activation of a larger relative fraction of µ receptors, and hence are more vulnerable to tolerance-associated reductions in receptor density than rate-increasing effects. Two sets of experiments were conducted to test this hypothesis. First, the effects of morphine on ICSS were examined after pretreatment with the irreversible µ antagonist ß-funaltrexamine to reduce the density of available µ receptors. Second, effects were examined for a range of µ opioids that varied in relative efficacy at µ receptors. The hypothesis predicted that (a) morphine, after ß-funaltrexamine treatment, or (b) low-efficacy µ agonists would mimic the effects of morphine tolerance to produce the reduced expression of rate-decreasing effects and enhanced expression of rate-increasing effects. Neither of these predictions were supported. These results indicate that µ agonist-induced facilitation and depression of ICSS may be mediated by distinct populations of µ receptors that respond differently to regimens of opioid exposure.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores Opioides mu
/
Tolerância a Medicamentos
/
Morfina
/
Entorpecentes
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article