Short communicationsInvolvement of the caudal granular insular cortex in alcohol self-administration in rats
Introduction
The insular cortex has been a region of great interest in addiction research since Naqvi et al. observed that stroke-induced damage to this region disrupts addiction to cigarette smoking [1]. The insular cortex, or insula, is responsible for interoception or the physiological condition of the body [2]. Understandably, insular activity has been observed in neuroimaging studies of anxiety, cognition, conscious urges, anxiety, pain, cognition, mood and substance abuse while animal models have also demonstrated a role for the insular cortex in behavioural aspects of multiple addictive substances (see [3] for review).
The granular, dysgranular, and agranular corticies are the three structurally and functionally distinct subregions that comprise the insula [4]. The caudal granular insular cortex (CGIC) integrates nociceptive [5] and unimodal viscerosensory [6] afferents from the thalamus along with those from the somatosensory cortex. It also primarily sends efferent projections back to those areas as well as to the caudate-putamen [7]. Through the dysgranular insular subregion, information initially integrated in the CGIC is relayed and further integrated before reaching the rostral agranular insular cortex (RAIC) [8]. Importantly, the granular insular cortex is the only insular subregion lacking projections to nuclei within the amygdala [8].
Recent findings by Seif et al. have established a role for glutamatergic neurons, projecting from the rostral agranular insular cortex (RAIC) to the nucleus accumbens, in quinine or electric footshock-based aversion-resistant alcohol intake but not for alcohol intake in the absence of such deterrents [9]. To our knowledge, no studies have yet to examine a role for the CGIC in alcohol self-administration. Thus, the current study examined whether the CGIC was involved in alcohol self-administration behavior, as we have previously observed for nicotine. The same intracranial manipulations used previously were used in the current study: bilateral infusions of γ-aminobutyric acid (GABA) receptor agonists, baclofen and muscimol.
Section snippets
Methods and results
Naive male Long-Evans rats (Charles River, Lachine, QC) weighing 300–325 g at the start of experiments were maintained on ∼20 g of rat chow daily and ad libitum water while in their home cages. Animals were single-housed in a temperature-controlled room on a 12 h reverse light cycle with all behavioral testing occurring during the dark phase.
Alcohol solution for oral self-administration was prepared by diluting 95% ethanol in tap water. A mixture of baclofen and muscimol (0.3 and 0.03 nmol/side,
Discussion
The results presented here demonstrate that inactivation of the CGIC is capable of attenuating operant responding for alcohol, as well as its overall intake, under an FR-3 schedule of reinforcement. Overall, these results appear similar to our prior findings with nicotine [11] and suggest that the CGIC may thus play a similar role in the self-administration of both drugs. An interesting finding was the increase in amount of wasted alcohol (i.e. mL of alcohol earned by the rat through operant
Conflicts of interest
Authors have none to declare.
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2022, NeuropharmacologyCitation Excerpt :In an attempt to look for causal evidence, we next aimed at perturbing insula activity to examine its role in voluntary alcohol drinking. Various techniques including neuronal inactivation, as well as chemogenetic and optogenetic manipulations have been employed to probe the role of insula in animal models of alcohol seeking and consumption (Campbell et al., 2019; Jaramillo et al., 2018a, 2018b; Pushparaj and Le Foll, 2015; Seif et al., 2013). Our experiments are principally in line with these studies, but were done in alcohol-preferring AA rats.
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2021, NeuropharmacologyCitation Excerpt :Further, amphetamine CPP memory in rat is disrupted by inhibiting protein synthesis in rAINS (AP+2.8) or rPINS (AP-0.5) (Contreras et al., 2012). Inhibiting AINS (Jaramillo et al., 2018c) or rPINS (−0.5) (Pushparaj and Le Foll, 2015) in rat reduces operant responding for alcohol, while nicotine but not food self-administration in rat is reduced by inhibiting PINS (AP-0.4) (Forget et al., 2010) or GC-AINS (AP+1.2) (Hollander et al., 2008). It is also interesting that different basic emotion states can be discerned from mouse facial expression (Dolensek et al., 2020), and while stimulating mouse AINS leads to pleasure-like responses, and stimulating PINS induces disgust, the individual PINS neuron activity encodes different facially-expressed emotions, including pleasure.