Blockade of dopamine D4 receptors in the paraventricular nucleus of the
hypothalamus inhibits food intake and behavioral satiety sequence in
rats
Abstract
With the escalating global prevalence of obesity, understanding eating
behavior is an imperative focus of research. Emerging evidence
underscores the central role of dopamine and its receptors in normal and
pathological regulation of food intake. Investigations have confirmed
the stimulatory effect of selective activation of D4 dopamine receptors
within the paraventricular nucleus of the hypothalamus on food intake.
This leads to the hypothesis that perturbations in hypothalamic
dopaminergic signaling pathways that regulate energy homeostasis may
potentially underlie the propensity for obesity-related excess caloric
consumption via a D4 Receptor-mediated mechanism. This study aims to
elucidate the effects of central administration of the D4 receptor
antagonist, L-745,870, on regulating food intake, satiety, and locomotor
activity. Here, we investigated the impact of intra-paraventricular
blockade of D4 receptors on standard food consumption, behavioral
satiety sequence, and locomotor activity in male Wistar rats. Our
results indicate that injection of L-745,870 at doses of 0.1 and 1 µg
induces a significant reduction in standard food intake within sixty
minutes of administration. At a dose of 0.1 µg, L-745,870 accelerated
the onset of postprandial satiety without a significant effect on
locomotor activity. Together, our results highlight the central role of
D4 receptors in the modulation of feeding behavior and satiety and
provide a potential avenue for using this compound for the development
of pharmacological interventions for obesity. The demonstrated efficacy
of L-745,870 in reducing food intake supports its potential therapeutic
utility in the broader context of obesity management.