Sucrose Abstinence and Environmental Enrichment Effects on Mesocorticolimbic DARPP32 in Rats

Abstract

Dopamine- and cAMP-regulated neuronal phosphoprotein 32 kDa (DARPP32) is a signaling molecule that could serve as a molecular switch, promoting or restraining sucrose seeking. We measured DARPP32 and pThr34 DARPP32 in the brains of male Long-Evans rats with a history of sucrose self-administration followed by 1 or 30 days of abstinence and exposure to either overnight (acute) or one month (chronic) environmental enrichment (EE). Brains were extracted following a 1 h cue reactivity test or no exposure to the test environment. Micropunches (prelimbic, infralimbic, and anterior cingulate areas of the medial prefrontal cortex, orbitofrontal cortex, dorsal striatum, nucleus accumbens, and ventral tegmental area) were then processed using Western blot. Abstinence increased, while EE decreased, sucrose seeking. DARPP32 and pThr34 DARPP32 levels were affected by testing, abstinence, and/or EE in most regions. Especially salient results were observed in the nucleus accumbens core, a region associated with relapse behaviors. Both acute and chronic EE reduced DARPP32 in the nucleus accumbens core and acute EE increased the ratio of phosphorylated to total DARPP32. Degree of DARPP32 phosphorylation negatively correlated with sucrose seeking. These findings demonstrate a potential role for DARPP32 in mediating the “anti-craving” effect of EE.

Incubation of food craving in rats: A review

“…Although Fos immunoreactivity (IR), a measure of recent neuronal activation, was not associated with incubation of chocolate-flavored pellets craving (Noye Tuplin & Holahan, 2019), we observed Fos IR "incubate" in regions involved in several aspects of reward processing (prelimbic, infralimbic, anterior cingulate, somatosensory cortices, dorsolateral striatum, core and shell of the nucleus accumbens, and central amygdala) . In contrast to the negative findings with brainderived neurotrophic factor and perineuronal nets described above, we recently reported abstinence-dependent changes in DARPP32 signaling (phosphorylation at Threonine 34) in ventral tegmental area, dorsolateral and dorsomedial striatum, and orbitofrontal cortex (Grimm et al, 2018). These are regions involved in reward, habit, and reward valuation (Wise, 2013).…”

“…Incubation of sucrose craving is attenuated by a dopamine D1 receptor antagonist. In contrast to the negative findings with brainderived neurotrophic factor and perineuronal nets described above, we recently reported abstinence-dependent changes in DARPP32 signaling (phosphorylation at Threonine 34) in ventral tegmental area, dorsolateral and dorsomedial striatum, and orbitofrontal cortex (Grimm et al, 2018). Rats were tested for sucrose cue-reactivity by allowing them to respond in extinction conditions including the tone+light cue either 1 or 30 days into sucrose abstinence.…”

Neurobehavioral Effects of Restricted and Unpredictable Environmental Enrichment in Rats

“…These mRNA analyses were performed in SH5, REE, and CEE rats that were not submitted to behavioral assessment. We extracted the nucleus accumbens, dorsal striatum, and hippocampus because 1) they are all involved in different phases of the motivational processes (e.g., attribution of incentive salience, the transition from motivation to action, and contextual encoding of reward cues) (Williams and Undieh, 2010;Anselme et al, 2013;Schultz, 2016); 2) they play a pivotal role on learning and memory (e.g., associative, procedural, and episodic/spatial memory) (Richard et al, 2013;Lisman et al, 2017); and 3) the EE-induced physiological and cellular effects have been well identified in those regions and especially in hippocampus (Bezard et al, 2003;Tipyasang et al, 2014;Brenes et al, 2016;Grimm et al, 2018;Scala et al, 2018;Ohline and Abraham, 2019).…”

Effects of Saccharin Consumption on Operant Responding for Sugar Reward and Incubation of Sugar Craving in Rats

“…The general experimental structure is shown in Figure 1 . Procedures for self-administration training, cue-tests, and consumption test were generally based on previous studies about the incubation of sugar craving [ 22 , 23 , 24 , 25 ], and the procedures for the yogurt phase were generally based on previous studies from the Purdue group [ 1 , 2 , 3 ]; however, details were adjusted for this study.…”

“…Cue-induced seeking behavior (cue-reactivity) is often used as a rodent model of craving [ 19 , 20 ]. Incubation of craving has been observed in rats with repeated experiences of sucrose self-administration [ 21 , 22 , 23 , 24 ]. In these studies, subjects were first trained to press a lever to obtain sucrose solution for successive daily sessions, in which each sucrose presentation was paired with a discrete compound cue (tone + light) and then tested after forced-abstinence of sucrose.…”