A reassessment of the role of serotonergic system in the control of feeding behavior

Abstract

The role of serotonergic system in the feeding behavior was appraised by electrolytic lesions in the dorsal raphe nucleus (DRN) and administration of para-chlorophenylalanine (PCPA, 3 mg/5 µl, icv). Chronic evaluations were accomplished through 120 and 360 days in PCPA-injected and DRN-lesioned rats, respectively. Acute food intake was evaluated in fasted rats and submitted to injection of PCPA and hydroxytryptophan (LHTP, 30 mg/kg, ip). DRN-lesioned rats exhibited 22-80% increase in food intake up to sixth month, whereas the obesity was evident and sustained by whole period. In PCPA-injected rats was observed an initial increase in the food intake followed by hypophagy from 25 th to 30 th day and a transitory increase of body weight from 5 th to 60 th day. In the acute study, the LHTP reverted partially the PCPA-induced increase in food intake of fasted rats suggesting a sustained capacity of decarboxylation of precursor by serotonergic neurons. Slow restoration of the levels of food intake in DRN-lesioned rats reveals a neuroplasticity in the systems that regulate feeding behavior. A plateau on the body weight curve in lesioned rats possibly represents the establishment of a new and higher set point of energetic balance.

<p>Selective Ablation of Descending Serotonin from the Rostral Ventromedial Medulla Unmasks Its Pro-Nociceptive Role in Chemotherapy-Induced Painful Neuropathy</p>

“…In inhibitor experiments, the selective Tph inhibitor para-chlorophenylalanine (PCPA, #C6506, Sigma) was dissolved in normal saline, and the p38 MAPK inhibitor SB203580 (#S8307, Sigma) was dissolved in 2% dimethyl sulfoxide (DMSO). 18,26,28,29 Immunohistochemistry Animals were anesthetized using 10% chloral hydrate (300 mg/kg, intraperitoneally) and perfused transcardially with 0.9% saline followed by 4% paraformaldehyde. The brain was removed, post-fixed in 4% paraformaldehyde, and immersed in a 10-30% sucrose gradient in phosphate buffer saline (PBS) at 4°C.…”

“…[14][15][16][17] Tryptophan hydroxylase (Tph) is the rate-limiting enzyme in 5-HT biosynthesis. 18 It has been reported that the transcription of Tph could be regulated by phosphorylation of p38 MAPK. 19 Recent studies have indicated that selectively depleting 5-HT in RVM neurons with regional ablation of Tph inhibited inflammatory and neuropathic pain.…”

Comparison of projections of the dorsal and median raphe nuclei, with some functional considerations

“…Central or peripheral manipulations that give rise to increased levels of 5-HT, particularly within appetite control centers of the hypothalamus, produce anorexic effects, while blocking 5-HT actions significantly enhances food intake [82,83]. While the precise influence of DR on feeding remains to be resolved, a recent study by Medeiros et al [84] found that electrolytic DR lesions or 5-HT depletion with the administration of p-chlorophenylalanine (PCPA) produced marked increases in food intake for a prolonged period of over 6 months. In addition, intra-DR injections of 8-OH-DPAT (5-HT 1A autoreceptor agonist that inhibits 5-HT cells) was shown to produce hyperphagia in rodents and non-human primates [85].…”

Estradiol increases Pet-1 and serotonin transporter mRNA in the midbrain raphe nuclei of ovariectomized rats

“…We focused our attention on the midbrain raphe nuclei (including the subnuclei of the DRN (dorsomedial (DRD), dorsolateral (DRL), ventromedial (DRV), and the median raphe nucleus (MRN)) because Pet-1 mRNA is restricted to this region (Hendricks et al, 1999) and this region has been implicated (by pharmacology and lesion studies) in the serotonergic control of food intake (Fletcher and Davies, 1990; Medeiros et al, 2005). The doses of EB were chosen because they produce reliable, anorexigenic effects in OVX rats, and the lower (2 μg) dose of EB models the pattern of plasma estradiol concentration observed in intact, cycling rats (Asarian and Geary, 2002; Geary and Asarian, 1999).…”