Chronic ethanol exposure leads to divergent control of dopaminergic synapses in distinct target regions

Abstract

Neuroadaptations following chronic exposure to alcohol are hypothesized to play important roles in alcohol-induced alterations in behavior, in particular increased alcohol drinking and anxiety like behavior. Dopaminergic signaling plays a key role in reward-related behavior, with evidence suggesting it undergoes modification following exposure to drugs of abuse. A large literature indicates an involvement of dopaminergic signaling in response to alcohol. Using a chronic inhalation model of ethanol exposure in mice, we have begun to investigate the effects of alcohol intake on dopaminergic signaling by examining protein levels of tyrosine hydroxylase (TH) and the dopamine transporter (DAT), as well as monoamine metabolites in three different target fields of three different dopaminergic nuclei. We have focused on the dorsal lateral bed nucleus of the stria terminalis (dBNST) because of the reported involvement of dBNST dopamine in ethanol intake, and the nucleus accumbens (NAc) and dorsal striatum because of their dense dopaminergic innervation. After either a chronic intermittent exposure (CIE) or continuous exposure (CCE) regimen, mice were killed, and tissue punches collected from the dBNST, NAc and striatum for Western analysis. Strikingly, we found divergent regulation of TH and DAT protein levels across these three regions that was dependent upon the means of exposure. These data thus suggest that distinct populations of catecholamine neurons may be differentially regulated by ethanol, and that ethanol and withdrawal interact to produce differential adaptations in these systems.

Chronic ethanol exposure increases inhibition of optically targeted phasic dopamine release in the nucleus accumbens core and medial shell ex vivo

“…Increased uptake rates have been reported in the NAc of mice (Rose et al 2016), rats (Budygin et al 2007) and monkeys (Siciliano et al 2016) following chronic ethanol exposure, and these findings are supported by increased DAT protein tissue expression (Healey et al 2008). Here we add to the consensus by showing increased uptake rates in the NAc core following a CIE vapor exposure paradigm.…”

Cannabinoid Receptors in the Bed Nucleus of the Stria Terminalis Control Cortical Excitation of Midbrain Dopamine CellsIn Vivo

“…There are no clear cytoarchitectural boundaries differentiating subaspects of the BNST. However, the BNST is well defined by a dense noradrenergic and dopaminergic innervation (Delfs et al, 2000;Healey et al, 2008). Thus, we examined projection from the BNST to the VTA using tract-tracing approach and by immunohistochemical staining for TH to reveal dopaminergic and noradrenergic fibers (Fig.…”

Chronic intermittent ethanol exposure reduces presynaptic dopamine neurotransmission in the mouse nucleus accumbens

“…For example, dopaminergic neurons in the VTA of ethanol-dependent rats exhibit reduced tonic and burst firing rates (Diana et al, 1993; Bailey et al, 2001; Shen, 2003; Shen et al, 2007) during withdrawal. Animals exposed to chronic ethanol also have decreased expression of tyrosine hydroxylase (TH) coupled with augmented levels of DA transporter (DAT) in the striatum (Rothblat et al, 2001; Healey et al 2008), consistent with an attenuation in DA signaling. Together, these observations suggest that there are multiple functional changes in DA regulation that reduce signaling during ethanol withdrawal.…”