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

Abstract

Chronic continuous cocaine administration for 3 days has been shown to upregulate the level of mu 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 (approximately 2.0 nM) was unchanged during the cocaine treatment.

Cocaine Modulates the Expression of Opioid Receptors and miR-let-7d in Zebrafish Embryos

“…1A) was altered during the different stages of embryonic development. These changes are in agreement with the observations of Azaryan et al (1998) [46] and Yuferov et al (1999) [47], who found changes in MOR after cocaine administration to rats. Since the analgesia produced by morphine is mainly due to its interaction with the MOR [1], the changes induced by cocaine in MOR expression could induce alterations in its function [14], [48] and therefore in its analgesic activity.…”

Cocaine seeking over extended withdrawal periods in rats: time dependent increases of responding induced by heroin priming over the first 3 months

“…Other studies have shown that endogenous opioid peptides and exogenous opiates regulate mesolimbic dopamine transmission (Kalivas et al 1983;Kalivas and Duffy 1987;Spanagel et al 1990;Vanderschuren et al 2001;De Vries and Shippenberg 2002). Furthermore, repeated cocaine exposure has been shown to regulate opioid receptors binding (Unterwald et al 1992;Turchan et al 1999) and opiate receptor mRNA expression in the rat brain (Spanagel et al 1990;Azaryan et al 1996Azaryan et al , 1998. Moreover, in cocaine addicts, upregulation of μ receptor binding persists up to 4 weeks after withdrawal from cocaine, and increases in μ receptor binding in several brain areas (the frontal, temporal and anterior cingulate cortices, and the amygdala) were found to correlate with the severity of cocaine craving during early withdrawal (Zubieta et al 1996).…”

Reward Processing by the Opioid System in the Brain

“…Generally, literature in the field suggests an increase in mu receptor gene expression in several brain structures. Levels of mu receptor mRNA were increased in the NAc and rostral cingulate cortex after chronic exposure to cocaine or after cocaine CPP, whereas no change was detected in the CPu (16, 210, 381, 397). One report showed no change in mu receptor transcripts in both dorsal and ventral striatal areas following a cocaine binge (18).…”