Incubation of nicotine seeking is associated with enhanced protein kinase A‐regulated signaling of dopamine‐ and cAMP‐regulated phosphoprotein of 32 kDa in the insular cortex

Abstract

A recent clinical study demonstrated that damage to the insular cortex can disrupt tobacco addiction. The neurobiological mechanisms for this effect are not yet understood. In this study we used an animal model of nicotine addiction to examine the possibility that changes in insular cortex levels of dopamine (DA)- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), a phosphoprotein enriched in DA neurons containing DA D1 receptors, may be associated with changes in vulnerability to nicotine addiction. Once rats acquired self-administration, they were given unlimited access to nicotine (0.01 mg/kg/infusion) for 23 h/day for a total of 10 days. Each infusion was paired with a visual cue (stimulus light) and auditory cue (sound of pump). Nicotine seeking, as assessed under a cue-induced reinstatement paradigm, and markers of DARPP-32 signaling, as assessed using western blot analysis, were examined in separate groups of rats at two different abstinent intervals: 1 and 7 days. Consistent with findings with other drugs of abuse, rats in the 7-day abstinence group took longer to extinguish and responded at higher levels during reinstatement testing as compared with rats in the 1-day reinstatement group. Relative to saline controls, rats in the 7-day but not the 1-day abstinence group had higher levels of DARPP-32 phosphorylated at the protein kinase A site in the insular cortex. These results demonstrate incubation of drug seeking following extended access to nicotine self-administration and suggest that enhanced protein kinase A signaling in the insular cortex via phosphorylation of DARPP-32 at Thr34 is associated with this effect.

Role of Central Amygdala Neuronal Ensembles in Incubation of Nicotine Craving

“…Results from two studies showed that the response to smokingassociated cues in humans and to nicotine-associated cues in rats progressively increases or incubates after withdrawal (Abdolahi et al, 2010;Bedi et al, 2011). In the human study, Bedi et al (2011) showed that nicotine-cue-induced subjective craving is higher after 35 withdrawal days than after 7 or 14 d. In the rat study, Abdolahi et al (2010) showed that, after nicotine selfadministration, extinction responding and subsequent cueinduced reinstatement after extinction are higher after 7 withdrawal days than after 1 d. The results of Abdolahi et al (2010) extend previous rat studies on "incubation of drug craving" after withdrawal from cocaine (Neisewander et al, 2000;Grimm et al, 2001), heroin (Shalev et al, 2001), methamphetamine (Shepard et al, 2004), or alcohol (Bienkowski et al, 2004.…”

Incubation of Methamphetamine and Palatable Food Craving after Punishment-Induced Abstinence

“…An analogous phenomenon, termed 'incubation of drug craving', was subsequently identified in rats, based on observations that time-dependent increases in cue-induced cocaine or heroin seeking occurred after withdrawal from these drugs (Grimm et al, 2001;Neisewander et al, 2000;Shalev et al, 2001). Subsequent studies have demonstrated that incubation of drug craving also occurs in rats with a history of nicotine, alcohol, or methamphetamine self-administration (Abdolahi et al, 2010;Bienkowski et al, 2004;Shepard et al, 2004).…”

Role of Dorsomedial Striatum Neuronal Ensembles in Incubation of Methamphetamine Craving after Voluntary Abstinence

“…In rats, drug seeking progressively increases after forced abstinence from cocaine (Tran-Nguyen et al, 1998;Grimm et al, 2001), heroin (Shalev et al, 2001), nicotine (Abdolahi et al, 2010), alcohol (Bienkowski et al, 2004), and methamphetamine self-administration, a phenomenon termed "incubation of drug craving" (Lu et al, 2004). These studies inspired clinical studies demonstrating the incubation of nicotine (Bedi et al, 2011), alcohol , cocaine (Parvaz et al, 2016), and methamphetamine (Wang et al, 2013) craving in humans.…”