Distinct Patterns of Neural Activation Associated with Ethanol Seeking: Effects of Naltrexone

Abstract

Background-Alcoholism, like other substance abuse disorders, is a chronically relapsing condition. Compared with other abused drugs, however, little is known about the neural mechanisms mediating ethanol (EtOH)-craving and -seeking behavior leading to relapse. This study, therefore, was conducted to identify candidate brain regions that are recruited by an EtOH-associated contextual stimulus (S + ). A secondary objective was to determine whether EtOH S + -elicited neural recruitment patterns are modified by the opiate antagonist naltrexone (NTX), a compound that reduces cueinduced craving in alcoholics and attenuates ethanol seeking in animal models of relapse.

Alcohol Relapse Induced by Discrete Cues Activates Components of AP-1 Transcription Factor and ERK Pathway in the Rat Basolateral and Central Amygdala

“…It has been shown that cocaine-and alcohol-paired discrete cues did not activate c-Fos expression in the CeA (Neisewander et al, 2000;Ciccocioppo et al, 2001;Dayas et al, 2007;Zhao et al, 2006). However, in the latter studies many extinction sessions were run prior to the final reinstatement session (a factor which could account for the discrepancies between the results of those studies and our data).…”

Roles of the Nucleus Accumbens and Amygdala in the Acquisition and Expression of Ethanol-Conditioned Behavior in Mice

“…For example, in a ethanol reinstatement model using a discriminative stimulus task, increased Fos expression was observed in the Acb (Dayas et al, 2007), in addition to the Acb, BLA, and CE in a separate study (Zhao et al, 2006). Furthermore, recent findings from an ethanol cue-induced reinstatement study found increases in BLA and CE activation in response to a discrete cue (Radwanska et al, 2007).…”

“…Such learning is important because it can alter physiological/behavioral responses, motivational states (e.g., craving), or expectancies that affect the probability, vigor, or cue-directed nature of ethanolseeking behavior (Krank, 1989(Krank, , 2003Cunningham, 1994Cunningham, , 1998Corbit and Janak, 2007). Pavlovian learning may be especially involved in triggering relapse to ethanol seeking after periods of abstinence or extinction (Krank and Wall, 1990;Katner and Weiss, 1999;Ciccocioppo et al, 2001Ciccocioppo et al, , 2002Ciccocioppo et al, , 2003Nie and Janak, 2003;Zironi et al, 2006;Dayas et al, 2007). Despite the prevalence of alcohol abuse and dependence, surprisingly little is known about the neural areas that mediate the acquisition and expression of ethanol-seeking behaviors.…”

“…In contrast, very few studies have addressed the neurocircuitry underlying conditioned effects of cues paired with ethanol. Two recent studies reported increased Fos expression in brain areas activated by exposure to cues previously associated with ethanol either as a discriminative stimulus in an operant selfadministration task (Dayas et al, 2007) or as a conditioned stimulus (CSϩ) in a pavlovian procedure (Hill et al, 2007). Only one previous study, however, has addressed the functional role of any brain area in the expression of behavior elicited by an ethanol-paired stimulus.…”

The Dorsal Subiculum Mediates the Acquisition of Conditioned Reinstatement of Cocaine-Seeking

“…Although a pivotal role of the hippocampus in conditioned responses to fearful stimuli and associative learning relevant for anxiety-related responses is well documented (Anagnostaras et al, 2001;LeDoux, 1992, 1994), the dorsal hippocampus (DH) is also known to have a role in contextual memory retrieval and the occasion-setting action of contextual stimuli (eg Holland and Bouton, 1999). Indeed, the DH has been implicated in the control of ethanol- (Dayas et al, 2007;Zhao et al, 2006) and cocaine-seeking (Franklin and Druhan, 2000;Fuchs et al, 2005;Neisewander et al, 2000) induced by contextual stimuli in reinstatement models. The subiculum, a related brain structure that receives the majority of hippocampal projections (Commins et al, 1998;Stewart, 1997;Witter and Groenewegen, 1990;Young et al, 1997), is hypothetized to participate in mediating associative learning and, thus, likely to play an important role in behavior controlled by environmental stimuli related to drugs of abuse.…”