Transient upregulation of μ opioid receptor mRNA levels in nucleus accumbens during chronic cocaine administration

Autor: Anahit V. Azaryan, John Rosenberger, Barbara J. Clock, Brian M. Cox
Rok vydání: 1998
Předmět:
Zdroj: Canadian Journal of Physiology and Pharmacology. 76:278-283
ISSN: 1205-7541
0008-4212
DOI: 10.1139/y98-023
Popis: Chronic continuous cocaine administration for 3 days has been shown to upregulate the level of µ opioid receptor (MOR) mRNA in the nucleus accumbens (n. acc.) of rat brain. Dopamine (DA) antagonists, SCH 23390, eticlopride, and nafadotride, blocked, and DA agonists, SKF 38393, R(+)-6-bromo-APB hydrobromide, and bromocriptine, mimicked the cocaine-induced upregulation of MOR mRNA, suggesting involvement of both subfamilies of DA receptors in the effect of cocaine. In the present study the time course of cocaine-induced and DA agonist induced alterations in the level of MOR mRNA in n. acc. has been determined and compared with the changes in the level of MOR binding sites. Male Sprague-Dawley rats were treated with saline, cocaine (50 mg ·kg-1 ·day-1), or DA agonists for periods between 24 and 336 h. Expression of MOR mRNA in n. acc. was estimated using quantitative competitive polymerase chain reaction assays following reverse transcription. The cocaine-induced upregulation of MOR mRNA in n. acc. was transient, developing 2 days after exposure, and peaking at 3 days with return to baseline levels by 4 days of chronic continuous cocaine treatment. The temporal characteristics of DA agonist induced increase in the levels of MOR mRNA in n. acc. were similar to those of cocaine, with maximum effect after 3 days of treatment. The density of [3H]DAMGO binding sites in n. acc. was 30% higher after 3 days of cocaine administration than in saline-treated control animals, but returned toward baseline levels after 4 days of cocaine treatment. No changes in the binding of [3H]DAMGO were detected after 7 or 14 days exposure to cocaine. The affinity of [3H]DAMGO to n. acc. membranes (~2.0 nM) was unchanged during the cocaine treatment.Key words: cocaine, dopamine, dopamine agonists, µ opioid receptor, nucleus accumbens, polymerase chain reaction.
Databáze: OpenAIRE