Selective serotonin receptor stimulation of the medial nucleus accumbens differentially affects appetitive motivation for food on a progressive ratio schedule of reinforcement

Abstract

Previously, we reported that stimulation of selective serotonin (5-HT) receptor subtypes in the nucleus accumbens shell differentially affected consumption of freely available food. Specifically, activation of 5-HT6 receptors caused a dose-dependent increase in food intake, while the stimulation of 5-HT1/7 receptor subtypes decreased feeding [34]. The current experiments tested whether similar pharmacological activation of nucleus accumbens serotonin receptors would also affect appetitive motivation, as measured by the amount of effort non-deprived rats exerted to earn sugar reinforcement. Rats were trained to lever press for sugar pellets on a progressive ratio 2 schedule of reinforcement. Across multiple treatment days, three separate groups (N = 8–10) received bilateral infusions of the 5-HT6 agonist EMD 386088 (at 0.0, 1.0 and 4.0 μg/0.5 μl/side), the 5-HT1/7 agonist 5-CT (at 0, 0.5, 1.0, or 4.0 μg/0.5 μl/side), or the 5-HT2C agonist RO 60-0175 fumarate (at 0, 2.0, or 5.0 μg/0.5 μl/side) into the anterior medial nucleus accumbens prior to a 1-hr progressive ratio session. Stimulation of 5-HT6 receptors caused a dose-dependent increase in motivation as assessed by break point, reinforcers earned, and total active lever presses. Stimulation of 5-HT1/7 receptors increased lever pressing at the 0.5 μg dose of 5-CT, but inhibited lever presses and break point at 4.0 μg/side. Injection of the 5- HT2C agonist had no effect on motivation within the task. Collectively, these experiments suggest that, in addition to their role in modulating food consumption, nucleus accumbens 5-HT6 and 5-HT1/7 receptors also differentially regulate the appetitive components of food-directed motivation.

Fluoxetine Epigenetically Alters the CaMKIIα Promoter in Nucleus Accumbens to Regulate ΔFosB Binding and Antidepressant Effects

“…This suggests that the antidepressant effects of these compounds are, at least in part, due to long-term cellular adaptations downstream, and perhaps far removed, from increased serotonin signaling. Multiple subtypes of serotonin receptors are expressed in NAc, including 5-HT 1/7 , 5-HT 2C , and 5-HT 6 receptors, and NAc-specific pharmacological manipulation of these individual receptor types alters multiple behaviors, including feeding (Pratt et al, 2012) and alcohol action (Andrade et al, 2011). Although the mechanisms that link increased serotonin signaling to epigenetic modifications at the CaMKIIa promoter remain virtually completely unknown, we have demonstrated previously that chronic, systemic administration of fluoxetine or chronic NAcspecific inhibition of histone deacetylases-both of which produce antidepressant-like behavioral actions-have strikingly similar effects on global patterns of gene expression in NAc .…”

Serotonin 1A, 1B, and 7 receptors of the rat medial nucleus accumbens differentially regulate feeding, water intake, and locomotor activity

“…Specifically, Jean et al (2007) reported that the 5-HT 4 receptor in the mouse nucleus accumbens is responsible for the hypophagic actions of systemic MDMA (Ecstasy) treatment. We have reported that stimulation of rat medial nucleus accumbens 5-HT 6 receptors increases food intake and enhances appetitive motivation for sugar reinforcement (Pratt et al , 2009, Pratt et al , 2012). In contrast, nucleus accumbens 5-HT 2C receptor agonism or blockade has little effect on food motivation.…”

The effects of nucleus accumbens μ-opioid and adenosine 2A receptor stimulation and blockade on instrumental learning

“…Since that time, the roles of multiple neurotransmitter systems within the NAcc have been characterized, demonstrating important roles for glutamate [58-60], GABA [61-63], dopamine [64], opioids [36, 52-54], acetylcholine [28, 65-67], and serotonin [68-71] receptors on appetitive and consummatory behaviors directed towards food. Though both adenosine and opioid systems of the NAcc have previously been shown to impact food intake, this is the first examination of the potential roles for A2A and μ-opioid receptors of this region on the learning of an operant response reinforced by food.…”