Feeding behaviour after injection of α-adrenergic receptor agonists into the median raphe nucleus of food-deprived rats

Abstract

This study investigated the participation of median raphe nucleus (MnR) α1-adrenergic receptors in the control of feeding behaviour. The α1-adrenergic agonist phenylephrine (PHE) and α2-adrenergic agonist clonidine (CLON) (at equimolar doses of 0, 6 and 20 nmol) were injected into the MnR of: a) rats submitted to overnight fasting (18 h); or b) rats maintained with 15 g of lab chow/day for 7 days. Immediately after the drug injections, the animals were placed in the feeding chamber and feeding and non-ingestive behaviours such as grooming, rearing, resting, sniffing and locomotion were recorded for 30 min. The results showed that both doses of PHE injected into the MnR of overnight fasted animals decreased food intake accompanied by an increase in the latency to start feeding. A reduction in feeding duration was observed only after treatment of the MnR with the 20 nmol dose of PHE. Both locomotion duration and sniffing frequency increased after injection with the highest dose PHE into the MnR. Feeding frequency and the other non-ingestive behaviours remained unchanged after PHE treatment in the MnR. Both doses of PHE injected into the MnR of food-restricted rats decreased food intake. This hypophagic response was accompanied by a decrease in feeding duration only after treatment of the MnR with the highest dose of PHE. The latency to start feeding and feeding frequency were not affected by injection of either dose of PHE into the MnR. While both doses of PHE increased sniffing duration, the highest dose of PHE increased resting duration and resting frequency. Treatment with CLON into the MnR did not affect feeding behaviour in either of the food deprivation conditions. The present results indicate the inhibitory functional role of α1-adrenergic receptors within the MnR on feeding behaviour.

α-1 Adrenoceptor Activation in the Dorsal Raphe Nucleus Decreases Food Intake in Fasted Rats

“…Thus, it is possible that activation of DR α-1 adrenoceptors by PHE results in 5-HT release in fasted animals, since facilitatory control of 5-HT release is attributed to these receptors (Bortolozzi and Artigas, 2003). In agreement with this suggestion, a study demonstrated that PHE injections into the median raphe nucleus (MR), another major serotonergic cell group with α-adrenoceptors (Adell and Artigas, 1999), also evoked hypophagia in fasted rats (Ribas et al, 2012). Also, serotonergic activity is low in food restricted rats and, especially in the DR, food restriction decreases the optical density of 5-HT positive neurons when compared to fed rats (Haider and Haleem, 2000;Kang et al, 2001).…”

“…Statistical analyses revealed that PHE 20 nmol injection in the xscp did not affect ingestive behaviors when compared to the intra-DR vehicle group ( Figures 3C,D ). Previous work reported that PHE injection of 20 nmol dose into median raphe nucleus (MR) decreased food intake in fasted rats ( Ribas et al, 2012 ). Thus, the effects on food intake could be the sum of the drug effects in these two nuclei due the close localization in the mesopontine tegmentum.…”

Cannabigerol is a novel, well-tolerated appetite stimulant in pre-satiated rats

“…Alternatively, CBG-induced hyperphagia may be mediated by its activity (to date only observed in vitro) as a highly potent agonist of α2-adrenoceptors (Cascio et al 2010 ). Consistent with this, stimulation of α2-adrenoceptors in the hypothalamic paraventricular nucleus has been shown to have hyperphagic effects in satiated rats (Wellman et al 1993 ; Taksande et al 2011 ), whilst administration of the α2-adrenoceptor agonist clonidine into the median raphe nucleus had orexigenic effects in free feeding (Mansur et al 2010 ) but not fasted or food-restricted rats (Ribas et al 2012 ). Whilst the above studies suggest that central α2-adrenoceptor activation may be involved in the hyperphagic activity of CBG, it should be noted that recent cardiovascular safety assays in dog did not reveal any effects on cardiovascular parameters (T. Hill, personal communication), indicating that α2-adrenoceptor agonism may not be the predominant action for CBG.…”