Original articleDistinct Patterns of Neural Activation Associated with Ethanol Seeking: Effects of Naltrexone
Section snippets
Subjects
Male Wistar rats (Charles River, Raleigh, North Carolina) weighing 180 to 200 g on arrival were housed three per cage in a temperature and humidity controlled vivarium on a reversed 12-hour light/dark cycle (lights off 8:00 am). Training and testing were conducted daily from 12:00 pm to 3:00 pm. All procedures were carried out in accordance with the NIH Guide for the Care and Use of Laboratory Animals and were approved by The Scripps Research Institute Institutional Animal Care and Use
Ethanol Self-Administration, Conditioning, and Extinction
All rats acquired responding reinforced by 10% ethanol and developed stable ethanol self-administration during the conditioning phase. The mean (± SEM) number of responses averaged across the three final sessions was 26 ± 3 during ethanol and 7 ± 1 during nonreward sessions (Figure 2A). Rats emitted 16 ± 2 responses during the first extinction session. All rats reached the extinction criterion within 10 days.
Behavioral Effects of Ethanol Cue Exposure and Modification by Naltrexone
Rats exposed to the ethanol S+ and pretreated with vehicle or NTX (S+/VEH) showed
Discussion
Confirming earlier findings (Ciccocioppo et al 2002, Ciccocioppo et al 2003, Katner and Weiss 1999, Liu and Weiss 2002), an olfactory stimulus (S+) conditioned to ethanol reward, but not a cue associated with nonreward (S−), elicited recovery of responding at a previously ethanol-paired lever. Exposure to the ethanol S+ and ensuing ethanol-seeking behavior was associated with activation of the Pre-L, Infra-L, and AC mPFC divisions; the NAC; and dorsal HIPPO, indicating that major components of
Conclusions
Ethanol-associated contextual stimuli elicit specific recruitment patterns within the mPFC, NAC, and HIPPO in rats similar to those produced by other abused drugs, as well as brain activation patterns evoked by ethanol cues in alcoholics (Grusser et al 2004, Maas et al 1998, Myrick et al 2004). The findings also reveal that the effects of the “anticraving” agent NTX on this recruitment profile are complex. While it must be taken into account that c-fos expression is not a comprehensive marker
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2021, Neuroscience and Biobehavioral ReviewsCitation Excerpt :PVT neurons express a variety of receptors including for corticotropin-releasing hormone, opioids, dopamine, neuropeptide S, VIP, and cannabinoid, among others (Colavito et al., 2015; Kirouac, 2015). PVT has been implicated in a diverse range of functions including arousal (Colavito et al., 2015), stress (Bhatnagar, 2003; Bhatnagar and Dallman, 1999; Bhatnagar et al., 2002; Hsu et al., 2014), fear (Beas et al., 2018; Do-Monte et al., 2015; Penzo et al., 2015; Zhu et al., 2018), appetitive learning (Otis et al., 2017, 2019; Zhu et al., 2018), incentive salience (Campus et al., 2019; Haight and Flagel, 2014; Haight et al., 2015, 2017), relapse to drug seeking (Dayas et al., 2007, 2008; Hamlin et al., 2009; James et al., 2011, 2010; James and Dayas, 2013; Marchant et al., 2010; Martin-Fardon and Boutrel, 2012; Matzeu et al., 2017, 2015), opiate withdrawal (Zhu et al., 2016), drinking and feeding (Barson et al., 2015; Ong et al., 2017). We suggest that PVT is implicated in these diverse functions because they each have in common the need for bistable selection as they involve competing motivational demands on the animal and PVT is a key component of the circuitry for this selection.