Role of insular cortex D1 and D2 dopamine receptors in nicotine self-administration in rats

Abstract

The insular cortex has been associated with the processing of rewarding stimuli and with the neural bases of drug addiction. Ischemic damage to the insula has been associated with decreased desire to smoke cigarettes. Which component of insular function is involved in the neural basis of cigarette smoking is not clear. Dopamine systems are crucial for the reinforcing value of addictive drugs. The DA projection from the ventral tegmental area to the nucleus accumbens (NAc) has been shown to be a vital pathway for the primary reinforcement caused by taking a variety of abused drugs. In the current set of studies, the roles of D1 and D2 receptors in the insular cortex in the self-administration of nicotine by rats were assessed. Adult female Sprague-Dawley rats were fitted with jugular catheters and given access to self-administer nicotine. Bilateral local infusion cannulae were implanted into the agranular insular cortex to locally administer D1 and D2 antagonists (SCH-23390 and haloperidol). Acute local infusions of the D1 antagonist SCH-23390 into the insula (1–2 μg/side) significantly decreased nicotine self-administration by more than 50%. Repeated infusions of SCH-23390 into the agranular insula caused continuing decreases in nicotine self-administration without signs of tolerance. In contrast, local infusions of the D2 antagonist haloperidol 0.5–2 μg/side did not have any discernable effect on nicotine self-administration. These studies show the importance of DA D1 systems in the insula for nicotine reward.

Involvement of the rostral agranular insular cortex in nicotine self-administration in rats

“…When examining the incubation enhanced cue-induced reinstatement of nicotine seeking, Abdolahi and colleagues (2010) observed an associated increase in the dopamine and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), a phosphoprotein enriched in neurons containing dopamine D1-subtype receptors, specifically within the RAIC but not the CGIC of rats [31]. Confirming the ability of direct RAIC manipulation to affect nicotine self-administration, Kutlu and colleagues (2013), found that bilateral infusions of D1, but not D2, antagonists into the RAIC were capable of decreasing nicotine self-administration in rats [16] similar to the effect found with GABA agonist-induced inactivation in the present study.…”

“…Within animal studies involving insular cortex manipulations, studies have demonstrated both a role for the CGIC [14,15,17,41,42] or RAIC [16,[43][44][45][46][47] or both [13,48] in addiction relevant behaviors. To our knowledge, only two studies thus far have compared manipulations of the CGIC vs. RAIC and found differential involvement in addiction-relevant behaviors.…”

“…As it receives afferents from the high-order [28] medial subdivision of the mediodorsal thalamic nucleus [29,30], along with those from multiple medial thalamic nuclei conveying motivational/affective aspects of peripheral stimuli, the RAIC is considered a high-order multimodal cortical region. The involvement of the RAIC has also been observed in certain models of nicotine addiction [16,31] and neural responses to nicotine exposure [32,33] in rodents.…”

“…correlated to immediate smoking cessation easily achieved without craving or relapse. Though many human imaging studies followed [12], animal models have been critical to examine the effects of manipulating insular cortex function in various aspects of nicotine addiction [13][14][15][16][17].…”

Prediction error and somatosensory insula activation in women recovered from anorexia nervosa

“…Primary location of DA neuron activity is measured in the ventral striatum and midbrain, but DA-mediated brain activation is also distributed across the prefrontal cortex, including the insula. 14 Within the brain reward circuitry DA has the role of responding to unexpected receipt or omission of rewards, acts as a learning signal and guides us to approach rewarding stimuli, including food. 9,15 Thus, the DA system could be involved in altered food approach or food avoidance in individuals with anorexia nervosa.…”