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

Adolescence is often portrayed as a period of enhanced sensitivity to reward, with long-lasting neurobiological changes upon reward exposure. However, we previously found that time-dependent increases in cue-induced sucrose seeking were more pronounced in rats trained to self-administer sucrose as adults than as adolescents. In addition, adult, but not adolescent sucrose self-administration led to a decreased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-Methyl-D-aspartate (AMPA/NMDA) ratio in the nucleus accumbens core, suggesting that long-lasting changes in glutamatergic transmission may affect adult processing of natural rewards. Here we tested whether altering glutamatergic transmission in the nucleus accumbens core via local injection of an mGluR2/3 agonist and antagonist affects cue-induced sucrose seeking following abstinence and whether this is different in the two age groups. Rats began oral sucrose self-administration training (10 days) on postnatal day (P) 35 (adolescents) or P70 (adults). Following 21 days of abstinence, rats received microinjections of the mGluR2/3 agonist LY379268 (0.3 or 1.0 µg/side) or vehicle into the nucleus accumbens core, and 15 min later cue-induced sucrose seeking was assessed. An additional group of rats trained as adults received nucleus accumbens core microinjections of the mGluR2/3 antagonist (RS)-α-Methyl-4-phosphonophenylglycine (MPPG) (0.12 or 0.5 µg/side). Confirming our previous results, adult rats earned more sucrose reinforcers, while sucrose intake per body weight was similar across ages. On abstinence day 22, local injection of the mGluR2/3 agonist LY379268 increased cue-induced sucrose seeking only in adult rats, and had no effect in adolescents. Local injections of the mGluR2/3 antagonist MPPG had no effect on sucrose seeking in adult rats. These data suggest an important developmental difference in the neural substrates of natural reward, specifically a difference in glutamatergic transmission in the accumbens in cue-induced responding for sucrose between adolescent and adult rats.

Supplemental morphine infusion into the posterior ventral tegmentum extends the satiating effects of self-administered intravenous heroin.

Rats learn to self-administer intravenous heroin; well-trained animals lever-press at a slow and regular pace over a wide range of intravenous doses. The pauses between successive earned infusions are proportional to the dose of the previous injection and are thought to reflect periods of drug satiety. Rats will also self-administer opiates by microinjection directly into sites in the posterior regions of the ventral tegmentum. To determine if the pauses between self-administered intravenous injections are due to opiate actions in posterior ventral tegmentum, we delivered supplemental morphine directly into this region during intravenous self-administration sessions in well-trained rats. Reverse dialysis of morphine into the posterior ventral tegmentum increased the intervals between earned injections. The inter-response intervals were greatest for infusion into the most posterior ventral tegmental sites, sites in a region variously known as the tail of the ventral tegmental area or as the rostromedial tegmental nucleus. These sites at which morphine prolongs inter-response intervals, correspond to the sites at which opiates have been found most effective in reinforcing instrumental behavior.