Microinjection of urotensin II into the pedunculopontine tegmentum leads to an increase in the consumption of sweet tastants.

The pedunculopontine tegmentum (PPTg) plays a role in processing multiple sensory inputs and innervates brain regions associated with reward-related behaviors. The urotensin II receptor, activated by the urotensin II peptide (UII), is selectively expressed by the cholinergic neurons of the PPTg. Although the exact function of cholinergic neurons of the PPTg is unknown, they are thought to contribute to the perception of reward magnitude or salience detection. We hypothesized that the activation of PPTg cholinergic neurons would alter sensory processing across multiple modalities (ex. taste and hearing). Here we had three aims: first, determine if cholinergic activation is involved in consumption behavior of palatable solutions (sucrose). Second, if so, distinguish the impact of the caloric value by using saccharin, a zero calorie sweetener. Lastly, we tested the UII-mediated effects on perception of acoustic stimuli by measuring acoustic startle reflex (ASR). Male Sprague-Dawley rats were bilaterally cannulated into the PPTg, then placed under food restriction lasting the entire consumption experiment (water ad lib.). Treatment consisted of a microinjection of either 1 µL of aCSF or 1 µL of 10 µM UII into the PPTg, and the rats were immediately given access to either sucrose or saccharin. For the remaining five days, rats were allowed one hour access per day to the same sweet solution without any further treatments. During the saccharin experiment rats were tested in a contact lickometer which recorded each individual lick to give insight into the microstructure of the consumption behavior. ASR testing consisted of a baseline (no treatment), treatment day, and two additional days (no treatment). Immediately following the microinjection of UII, consumption of both saccharin and sucrose increased compared to controls. This significant increase persisted for days after the single administration of UII, but there was no generalized arousal or increase in water consumption between testing sessions. The effects on ASR were not significant. Activating cholinergic PPTg neurons may lead to a miscalculation of the salience of external stimuli, implicating the importance of cholinergic input in modulating a variety of behaviors. The long-lasting effects seen after UII treatment support further research into the role of sensory processing on reward related-behaviors at the level of the PPTg cholinergic neurons.

Appetite-suppressing effects of urotensin I and corticotropin-releasing hormone in goldfish (Carassius auratus).

Fish urotensin I (UI), a member of the corticotropin-releasing hormone (CRH) family of peptides, is a potent inhibitor of food intake in mammals, yet the role of UI in the control of food intake in fish is not known. Therefore, to determine the acute effects of UI on appetite relative to those of CRH, goldfish were given intracerebroventricular (i.c.v.) injections of carp/goldfish UI and rat/human CRH (0.2-200 ng/g) and food intake was assessed for a 2-hour period after the injection. UI and CRH both suppressed food intake in a dose-related manner and UI (ED50 = 3.8 ng/g) was significantly more potent than CRH (ED50 = 43.1 ng/g). Pretreatment with the CRH receptor antagonist, alpha-helical CRH(9-41), reversed the reduction in food intake induced by i.c.v. UI and CRH. To assess whether endogenous UI and CRH modulate fish appetite, goldfish were given intraperitoneal implants of the glucocorticoid receptor antagonist, RU-486 (50 and 100 microg/g), or the cortisol synthesis inhibitor, metyrapone (100 and 200 microg/g), and food intake was monitored over the following 72 h. Fish treated with either RU-486 or metyrapone were characterized by a sustained and dose-dependent reduction in food intake. Pretreatment with i.c.v. implants of alpha-helical CRH(9-41) partially reversed the appetite-suppressing effects of RU-486 and metyrapone. In a parallel experiment, the effects of RU-486 (100 microg/g) and metyrapone (200 microg/g) intraperitoneal implants on brain UI and CRH gene expression were assessed. Relative to sham-implanted controls, fish treated with RU-486 or metyrapone had elevated UI mRNA levels in the hypothalamus and CRH mRNA levels in the telencephalon-preoptic brain region. Together, these results suggest that UI is a potent anorectic peptide in the brain of goldfish and that endogenous CRH-related peptides can play a physiological role in the control of fish appetite.