Long-term alcohol consumption alters dorsal striatal dopamine release and regulation by D2 dopamine receptors in rhesus macaques

Abstract

The dorsal striatum (DS) is implicated in behavioral and neural processes including action control and reinforcement. Alcohol alters these processes in rodents, and it is believed that the development of alcohol use disorder involves changes in DS dopamine signaling. In nonhuman primates, the DS can be divided into caudate and putamen subregions. As part of a collaborative effort examining the effects of long-term alcohol self-administration in rhesus macaques, we examined DS dopamine signaling using fast-scan cyclic voltammetry. We found that chronic alcohol self-administration resulted in several dopamine system adaptations. Most notably, dopamine release was altered in a sex- and region-dependent manner. Following long-term alcohol consumption, male macaques, regardless of abstinence status, had reduced dopamine release in putamen, while only male macaques in abstinence had reduced dopamine release in caudate. In contrast, female macaques had enhanced dopamine release in the caudate, but not putamen. Dopamine uptake was also enhanced in females, but not males (regardless of abstinence state). We also found that dopamine D2/3 autoreceptor function was reduced in male, but not female, alcohol drinkers relative to control groups. Finally, we found that blockade of nicotinic acetylcholine receptors inhibited evoked dopamine release in nonhuman primates. Altogether, our findings demonstrate that long-term alcohol consumption can sex-dependently alter dopamine release, as well as its feedback control mechanisms in both DS subregions.

Distinct sub-second dopamine signaling in dorsolateral striatum measured by a genetically-encoded fluorescent sensor

“…Then a stainless steel twisted bipolar stimulating electrode (P1 Technologies) was placed on the tissue surface near the area of dLight expression. For simultaneous photometry-voltammetry recordings, carbon fiber electrodes (CFE) were fabricated as previously described (Salinas et al, 2016; Salinas et al, 2021) and placed in the tissue in the center of the recording region of interest under 4X magnification. Slices were then visualized with 40X objective (0.8 NA) and the field of view (∼180um x 180um) was adjusted so the stimulating electrode was just outside the field of view and the CFE was in the center of the field of view.…”

“…A mechanical shutter (Uniblitz V25) was used to limit exposure to fluorophore-exciting light to discrete periods and minimize photobleaching of the dLight between recordings. FSCV recordings were carried out as previously described (Sgobio et al, 2014; Salinas et al, 2016; Sgobio et al, 2019; Salinas et al, 2021). Briefly, a triangle wave form voltage was applied to the CFE beginning at -0.4V to +1.2V and back to -0.4V.…”

Striatal µ-Opioid Receptor Activation Triggers Direct-Pathway GABAergic Plasticity to Induce Negative Affect

“…The emergence of hyperkatifeia after repeated opioid exposure is linked to a reduction in dopaminergic function ( Diana, 2011 ; Koob and Volkow, 2010 ). Withdrawal from chronic morphine exposure decreases dopamine release in the nucleus accumbens and dorsal striatum ( Ashok et al., 2017 ; Pothos et al, 1991 ; Salinas et al, 2021 ). We found that fentanyl IVSA reduced the spontaneous firing of SNc dopaminergic neurons.…”

Linking Ethanol-Addictive Behaviors With Brain Catecholamines: Release Pattern Matters

“…The effect of ethanol to increase the concentration of DA in the mesolimbic system has been known since the late 1980s ( Imperato and Di Chiara, 1986 ). To date, the studies using animal models have provided advanced characterization of the DA implication in neurobiological effects of ethanol, while clinical studies have concurred with a clarification of the involvement of DA in AUD ( Charlet et al, 2013 ; Söderpalm and Ericson, 2013 ; Chen et al, 2018 ; Salinas et al, 2021 ). On the other hand, both animal and human studies have also demonstrated that dysregulation of the NE system, which is tightly linked with arousal and stress response, can also be a key component of the AUD pathophysiology ( Haass-Koffler et al, 2018 ).…”