Time-dependent decreases in nucleus accumbens AMPA/NMDA ratio and incubation of sucrose craving in adolescent and adult rats

Abstract

Rationale and objectiveThere is evidence that cue-induced sucrose seeking progressively increases after cessation of oral sucrose self-administration (incubation of sucrose craving) in both adolescent and adult rats. The synaptic plasticity changes associated with this incubation at different age groups are unknown. We assessed whether incubation of sucrose craving in rats trained to self-administer sucrose as young adolescents, adolescents, or adults is associated with changes in 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid (AMPA)/N-methyl-d-aspartate (NMDA) ratio (a measure of postsynaptic changes in synaptic strength) in nucleus accumbens.MethodsThree age groups initiated oral sucrose self-administration training (10 days) on postnatal day (P) 35 (young adolescents), P42 (adolescents), or P70 (adults). They were then tested for cue-induced sucrose seeking (assessed in an extinction test) on abstinence days 1 and 21. Separate groups of rats were trained to self-administer sucrose or water (a control condition), and assessed for AMPA/NMDA ratio in nucleus accumbens on abstinence days 1–3 and 21.ResultsAdult rats earned more sucrose rewards, but sucrose intake per body weight was higher in young adolescent rats. Time-dependent increases in cue-induced sucrose seeking (incubation of sucrose craving) were more pronounced in adult rats, less pronounced in adolescents, and not detected in young adolescents. On abstinence day 21, but not days 1–3, AMPA/NMDA ratio in nucleus accumbens were decreased in rats that self-administered sucrose as adults and adolescents, but not young adolescents.ConclusionsOur data demonstrate age-dependent changes in magnitude of incubation of sucrose craving and nucleus accumbens synaptic plasticity after cessation of sucrose self-administration.

The Central Amygdala Nucleus is Critical for Incubation of Methamphetamine Craving

“…It is well established that extended drug access causes different physiological and behavioral changes than limited drug access (Ahmed and Kenny, 2011; Koob and Le Moal, 2001). Additionally, there is evidence from incubation of reward-craving studies that adult-onset selfadministration is associated with different physiological and behavioral changes than juvenile-and adolescent-onset selfadministration (Counotte et al, 2014;Doherty et al, 2013;Li and Frantz, 2009). …”

Nucleus accumbens injections of the mGluR2/3 agonist LY379268 increase cue-induced sucrose seeking following adult, but not adolescent sucrose self-administration

“…Adolescent rats started sucrose self-administration at postnatal day (P)35, while adult rats were P70 when self-administration training started. Note that the group that was called “Young adolescents” in our previous paper (Counotte et al, 2014) is now called “Adolescents” as we decided to only look in the two extreme groups in the present study. Rats were housed two per cage under reversed lighting conditions (lights on at 7PM) for the duration of the sucrose self-administration experiment.…”

“…Adolescence is a period of continued brain development (Casey et al, 2010, Counotte et al, 2011b, Blakemore and Robbins, 2012) which renders individuals with different reward sensitivity and altered long-lasting consequences of exposure to rewards compared to reward exposure during adulthood (Counotte et al, 2011a, Counotte et al, 2014). Previously, we showed that time-dependent increases in cue-induced sucrose seeking (incubation of sucrose craving) were more pronounced in adult rats that started self-administration at postnatal day (P)70 compared to adolescent rats that started at P35 (Counotte et al, 2014).…”

“…Previously, we showed that time-dependent increases in cue-induced sucrose seeking (incubation of sucrose craving) were more pronounced in adult rats that started self-administration at postnatal day (P)70 compared to adolescent rats that started at P35 (Counotte et al, 2014). In addition, we found that AMPA/NMDA ratio in nucleus accumbens core was decreased after 21 days of abstinence in rats that self-administered sucrose as adults, but not adolescents (Counotte et al, 2014).…”

“…Previously, we showed that time-dependent increases in cue-induced sucrose seeking (incubation of sucrose craving) were more pronounced in adult rats that started self-administration at postnatal day (P)70 compared to adolescent rats that started at P35 (Counotte et al, 2014). In addition, we found that AMPA/NMDA ratio in nucleus accumbens core was decreased after 21 days of abstinence in rats that self-administered sucrose as adults, but not adolescents (Counotte et al, 2014). This is the opposite of what was found following cocaine self-administration, where the AMPA/NMDA ratio is increased in accumbens shell medium spiny neurons (MSNs) (Conrad et al, 2008) and blockade of glutamate receptors decreases cue-induced cocaine seeking.…”