Buprenorphine is a weak dopamine releaser relative to heroin, but its pretreatment attenuates heroin‐evoked dopamine release in rats

Abstract

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A conditioned place preference for heroin is signaled by increased dopamine and direct pathway activity and decreased indirect pathway activity in the nucleus accumbens

“…Buprenorphine is used for opioid replacement therapy due to its ability to weakly activate mu opioid receptor signaling and prevent the binding of other opioids (e.g., heroin), and was recently shown to occlude heroin-evoked DA release into the NAc (Isaacs et al, 2020). To determine whether buprenorphine could similarly prevent the acquisition of heroin CPP, rats underwent a modified CPP procedure with 0 or 0.2 mg/kg buprenorphine given 10 min prior to each conditioning session ( Figure 7 A ).…”

“…In our final experiment, we show that pretreatment with buprenorphine during conditioning blocked the development of a heroin CPP and associated Fos activity in the NAc. Although buprenorphine weakly activates mu opioid receptors to mildly elevate DA release, it also prevents heroin from binding to the same receptors and driving larger phasic DA release (Isaacs et al, 2020). The buprenorphine dose used in the present study was selected based on a previous report that described a bell-shaped curve for buprenorphine-stimulated DA release into the NAc: significant increases in DA release with 0.01 – 0.04 mg/kg buprenorphine, but no change in DA release with 0.18 – 0.7 mg/kg buprenorphine (Isaacs et al, 2020).…”

“…Although buprenorphine weakly activates mu opioid receptors to mildly elevate DA release, it also prevents heroin from binding to the same receptors and driving larger phasic DA release (Isaacs et al, 2020). The buprenorphine dose used in the present study was selected based on a previous report that described a bell-shaped curve for buprenorphine-stimulated DA release into the NAc: significant increases in DA release with 0.01 – 0.04 mg/kg buprenorphine, but no change in DA release with 0.18 – 0.7 mg/kg buprenorphine (Isaacs et al, 2020). Moreover, twice daily injections of 0.1 – 0.4 mg/kg buprenorphine were sufficient to significantly attenuate cocaine self-administration in rats, with no differences observed between 0.1 and 0.4 mg/kg (Carroll and Lac, 1992).…”

A Conditioned Place Preference for Heroin Is Signaled by Increased Dopamine and Direct Pathway Activity and Decreased Indirect Pathway Activity in the Nucleus Accumbens

“…Buprenorphine is used for opioid replacement therapy because of its ability to weakly activate m opioid receptor signaling and prevent the binding of other opioids (e.g., heroin), and was recently shown to occlude heroin-evoked DA release into the NAc (Isaacs et al, 2020). To determine whether buprenorphine could similarly prevent the acquisition of heroin CPP, rats underwent a modified CPP procedure with 0 or 0.2 mg/kg buprenorphine given 10 min before each conditioning session (Fig.…”

“…Disrupting opioid signaling prevents development of heroin CPP In our final experiment, we show that pretreatment with buprenorphine during conditioning blocked the development of a heroin CPP and associated Fos activity in the NAc. Although buprenorphine weakly activates m opioid receptors to mildly elevate DA release, it also prevents heroin from binding to the same receptors and driving larger phasic DA release (Isaacs et al, 2020). The buprenorphine dose used in the present study was selected based on a previous report that described a bell-shaped curve for buprenorphine-stimulated DA release into the NAc, with significant increases in DA release with 0.01-0.04 mg/kg buprenorphine, but no change in DA release with 0.18-0.7 mg/kg buprenorphine (Isaacs et al, 2020).…”