κ-Opioid receptor modulation of accumbal dopamine concentration during operant ethanol self-administration

Abstract

Our study examined ethanol self-administration and accumbal dopamine concentration during κ-opioid receptor (KOPr) blockade. Long-Evans rats were trained to respond for 20 min of access to 10% ethanol (with sucrose) over 7 days. Rats were injected s.c. with the long-acting KOPr antagonist, nor-binaltorphimine (NOR-BNI; 0 or 20 mg/kg) 15-20 h prior to testing. Microdialysis revealed a transient elevation in dopamine concentration within 5 min of ethanol access in controls. NOR-BNItreated rats did not exhibit this response, but showed a latent increase in dopamine concentration at the end of the access period. The rise in dopamine levels correlated positively with dialysate ethanol concentration but not in controls. NOR-BNI did not alter dopamine levels in rats self-administering 10% sucrose. The transient dopamine response during ethanol acquisition in controls is consistent with previous results that were attributed to ethanol stimulus cues. The altered dopamine response to NOR-BNI during ethanol drinking suggests that KOPr blockade temporarily uncovered a pharmacological stimulation of dopamine release by ethanol. Despite these neurochemical changes, NOR-BNI did not alter operant responding or ethanol intake, suggesting that the KOPr is not involved in ethanol-reinforced behavior under the limited conditions we studied.

Pharmacological Evidence for a Motivational Role of κ-Opioid Systems in Ethanol Dependence

“…These results are consistent with the hypothesized upregulation of dynorphin systems observed following chronic ethanol as suggested by decreased mRNA for k-opioid receptors in the NAc and VTA (Rosin et al, 1999), as well as increased expression of dynorphin B in the NAc (Lindholm et al, 2000). The present data are also consistent with previous research which found that nor-BNI did not affect nondependent ethanol self-administration (Doyon et al, 2006) or consumption of ethanol within the context of the alcohol deprivation effect (Holter et al, 2000).…”

Affective Cue-Induced Escalation of Alcohol Self-Administration and Increased 22-kHz Ultrasonic Vocalizations during Alcohol Withdrawal: Role of Kappa-Opioid Receptors

“…DYN's relationship with alcohol and other drugs stems from its ability to modulate other neurotransmitters such as dopamine (DA), GABA, glutamate, and serotonin. Activation of the DYN/KOR system has been found to modify DA in the Acb following cocaine (Thompson et al, 2000) and ethanol use (Doyon et al, 2006). The DYN/KOR system also modulates dopaminergic neurons projecting to the prefrontal cortex (Margolis et al, 2006).…”

Accumbens Homer2 Overexpression Facilitates Alcohol-Induced Neuroplasticity in C57BL/6J Mice

“…As the effect of chronic alcohol consumption upon mGluR1/Homer2a/b/NR2b expression is enduring (Figure 1), this neuroadaptation may underlie the development of excessive alcohol intake, a defining feature of alcoholism, as well as contribute to the chronic, relapsing nature of this disease. Doyon et al, 2003Doyon et al, , 2004Doyon et al, , 2006Gonzales and Weiss, 1998;Melendez et al, 2002;Middaugh et al, 2003;Szumlinski et al, 2007;Weiss et al, 1993) and sensitizes the capacity of alcohol to elevate NAC glutamate . While neither Homer1 nor Homer2 proteins appear to be necessary for the regulation of NAC basal dopamine content, deletion of Homer1 or Homer2 produces a number of glutamatergic abnormalities within this region that have been implicated in regulating sensitivity to several drugs of abuse (Szumlinski et al, 2006c).…”