Stimulation of nucleus accumbens 5-HT₆ receptors increases both appetitive and consummatory motivation in an effort-based choice task

Abstract

Activity of the serotonin 6(5-HT₆) receptor impacts food intake and body weight in animal models and has also shown potential as a target for treatment of anhedonia, a symptom of major depressive disorder. The nucleus accumbens (NAc) is a key region involved in motivational processes and has been implicated in the neural mechanisms underlying anhedonia. Here, we assessed the potential role that 5-HT₆ receptors in the NAc play in regulating motivation towards food. Rats received surgical implantation of guide cannulas above the NAc shell. On testing days, they were injected with either the selective 5-HT₆ agonist EMD 386088 (at 0.0, 1.0, and 4.0 mg/0.5 mL/side) or the 5-HT₆ antagonist SB 252585 (at 0, 1.0, and 4.0 µg/0.5 µL/side) prior to completing a 1-h long effort-based choice task. The task simultaneously examined the impact of NAc 5-HT₆ receptor manipulation on appetitive motivation, measured as the breakpoint for earning a preferred sugar pellet in a progressive ratio task, and consummatory motivation, quantified as the grams of freely-available rat chow consumed during the session. Stimulation of NAc 5-HT receptors significantly increased both appetitive and consummatory motivation as assessed in this effort-based choice task. In contrast, 5-HT₆ antagonism did not affect break point nor the consumption of the freely-available chow. These data suggest that 5-HT₆ receptors are functional within the NAc, that their stimulation increases motivated behavior, and that they may therefore be a viable target for the treatment of anhedonia and disorders that inhibit motivational processes.