Differential adaptive properties of accumbens shell dopamine responses to ethanol as a drug and as a motivational stimulus

Abstract

Non-adaptive activation of dopamine transmission in the nucleus accumbens shell by drugs of abuse has been attributed a fundamental role in the mechanism of drug addiction. In order to test this hypothesis, we compared in the same subject the effect of an addictive drug (ethanol) and of taste stimuli, including ethanol's own taste, on dialysate dopamine in the nucleus accumbens shell as an estimate of dopamine transmission and on taste reactivity as an expression of motivational valence. Ethanol was also monitored in the dialysates. In naive rats, intraoral infusion of a 20% sucrose + chocolate solution elicited a monophasic increase of dialysate dopamine immediately after the intraoral infusion. In contrast, intraoral infusion of 10% ethanol, 10% ethanol + 20% sucrose or 10% ethanol + 20% sucrose + chocolate solutions elicited a biphasic increase of nucleus accumbens dopamine with an early taste-related rise and a late rise related to dialysate ethanol. Pre-exposure to the ethanol solutions 24 h before resulted in the absence of the early dopamine rise and permanence of the late dopamine rise. This late dopamine rise was actually increased as compared with that of the nonpre-exposed group when sucrose-containing ethanol solutions were tested. The results indicate that single trial pre-exposure to the ethanol solutions differentially affects the responsiveness of nucleus accumbens shell dopamine to the direct intracerebral action of ethanol and to the effect of its taste with potentiation, or no change of the first and abolition of the second. These observations point to the existence of major differences in the adaptive regulation of nucleus accumbens dopamine transmission in the shell after drug as compared with taste reward. These differences, in turn, are consistent with a role of nucleus accumbens shell dopamine in the mechanism of the behavioural effects of addictive drugs.

Alcohol Preference Influences the Subthalamic Nucleus Control on Motivation for Alcohol in Rats

“…Interestingly, ethanol elicits a biphasic increase of dopamine in the NAC (nucleus accumbens) shell. The first increase, related to taste reaction, undergoes habituation after the first exposure (as also observed with food), whereas the second increase, related to the increase on dialysate ethanol, remains unchanged at the second exposure (as also observed with psychostimulant drugs) (Bassareo et al, 2003;Di Chiara, 2002). Ethanol thus seems to act on the dopaminergic system in the NAC shell both like a natural reward and like a drug of abuse.…”

“…In the limbic circuit, the NAC, the VP (ventral pallidum), and the prefrontal cortex are known to be involved in ethanol reinforcement (Bassareo et al, 2003;Doyon et al, 2003;Samson and Czachowski, 2003). The limbic areas of the prefrontal cortex activate the STN, either by a direct excitatory input (the so-called 'hyperdirect pathway') or by an indirect disinhibitory pathway linking the NAC core and the STN via the VP (Maurice et al, 1998a, b).…”

“…In addition to their involvement in motor functions, the basal ganglia nuclei are involved in coding reward prediction and reward delivery (Arkadir et al, 2004;Darbaky et al, 2005;Hassani et al, 2001;Hollerman et al, 1998) and in the reinforcing properties of alcohol (Bassareo et al, 2003;Melendez et al, 2004). Within the cortico-basal ganglia-thalamocortical limbic loop, the subthalamic nucleus (STN) is a key structure that may modulate the basal ganglia outflow (Turner et al, 2001).…”

Chronic psychosocial stress causes delayed extinction and exacerbates reinstatement of ethanol-induced conditioned place preference in mice

“…At the serotoninergic level, chronic social defeat increased 5-HT 1B receptor mRNA levels in the rostral nucleus accumbens shell (Furay et al 2011). This brain region is highly involved in the rewarding properties of drugs of abuse in general and ethanol in particular (Bassareo et al 2003). Consequently, 5-HT 1B receptor expression increase in this particular region may facilitate chronic social stress-induced susceptibility to the rewarding aspects of ethanol.…”

Involvement of nucleus accumbens dopamine D1 receptors in ethanol drinking, ethanol-induced conditioned place preference, and ethanol-induced psychomotor sensitization in mice

“…Nevertheless, the neurobiological and molecular bases for ethanol action on the brain and addiction processes are poorly understood. Dopamine is widely recognized as a key neurotransmitter signal involved in drugs of abuse reward, and the dopaminergic system is believed to play a crucial role in the reinforcing properties of ethanol consumption (Badanich et al 2007;Bassareo et al 2003;Di Chiara 1997;Grace 2000;Herz 1997;Koob and Weiss 1992;Oreland et al 2011;Phillips and Shen 1996). However, the dopamine system is very complex and the role of the various dopaminergic receptor subtypes has been difficult to tease apart.…”