Nitric oxide and l-arginine have mixed effects on mammalian feeding in condition of a high motivation to feed.

Feeding inhibition caused by satiation in rats is partially mediated by the unconventional neurotransmitter nitric oxide (NO). Thus, in satiated rats blocking NO production increases feeding, and treatment with the NO precursor l-arginine or with an NO donor reduces feeding beyond that caused by satiation. Do NO and l-arginine also inhibit feeding when feeding motivation is high? When feeding motivation in satiated animals was hedonically increased by offering a highly attractive food, blocking NO production reduced the quantity eaten, rather than increasing it, indicating that hedonic aspects of food are partially mediated by NO. Increasing NO via an NO donor or l-arginine did not further increase the quantity eaten, indicating a ceiling effect. The NO donor, but not l-arginine, also decreased some motivation-dependent parameters of feeding. When feeding motivation was increased by hunger, quantities of food eaten were unaffected by an NO donor, blocker or precursor, with only the blocker of NO production affecting feeding patterning. We also examined effects on feeding of dissolving l-arginine in drinking water over 3 weeks. Chronic l-arginine administration had different effects during the first and in subsequent weeks, increasing feeding at first, but not later. The data indicate that NO has complex, state dependent effects on both the quantity of food eaten, and on patterns of feeding, probably reflecting different sites and mechanisms of action in the nervous system.

Nitric oxide and l-arginine regulate feeding in satiated rats.

Nitric Oxide (NO) and its precursor l-arginine were found to inhibit feeding in rats with a low motivation to eat, as they do in Aplysia. In rats that are relatively satiated, treatment with an NO blocker increased feeding, and treatment with an NO donor or with either of 2 doses of l-arginine inhibited feeding. NO and l-arginine modulated several parameters of feeding, such as the total duration of appetitive behaviors, the time spent feeding, the quantity of food eaten and the number of feeding bouts. The inhibitory effect of l-arginine on feeding could not be attributed to changes in locomotion. These data indicate that satiation is partially mediated by increased production of NO. NADPH-Diaphorase histochemical staining, which is specific for tissues actively producing NO, showed significantly greater staining in satiated compared to hungry rats in all 4 hypothalamic nuclei (paraventricular and arcuate nuclei, lateral and ventromedial hypothalamus) that were examined. l-arginine may act as a regulator of feeding by controlling NO production in several hypothalamic nuclei, specifically under condition of a low feeding motivation.

Effects of cannabidiol in males and females in two different rat models of depression.

The current study explores the therapeutic potential of Cannabidiol (CBD), a compound in the Cannabis plant, using both sexes of 2 "depressive-like" genetic models, Wistar Kyoto (WKY) and Flinders Sensitive Line (FSL) rats. Rats ingested CBD (30 mg/kg) orally. In the saccharin preference test, following a previous report of a pro-hedonic effect of CBD in male WKY, we now found similar results in female WKY. CBD also decreased immobility in the forced swim test in males (both strains) and in female WKY. These findings suggest a role for CBD in treating mental disorders with prominent symptoms of helplessness and anhedonia.

Maternal testosterone and reproductive outcome in a rat model of obesity.

Global sex differences in obesity rates are persistent, suggesting the involvement of sex steroids. In addition, adipose tissue is a metabolic site for steroidogenesis. Here, we compared female reproductive parameters in a rat model of obesity, with the same parameters in its lean control strain, and tested for an association with integrated measures of corticosterone and testosterone. Steroids were extracted and quantified from 17 Otsuka Long Evans Tokushima Fatty (OLETF; an animal model for obesity) and 13 Long Evans Tokushima Otsuka (LETO; the lean control strain) hair samples that were collected after weaning offspring. The obese OLETF mothers had higher hair testosterone levels than the control LETO strain. Overall, testosterone, but not corticosterone, predicted litter sex ratios. Younger mothers with large litters and older mothers with small litters tended to have the highest sex ratios (i.e., male-biased litters). In the lean LETO strain, but not in the obese OLETF, maternal testosterone was positively associated with litter size and number of male pups. Corticosterone did not differ between the two strains and was not associated with testosterone or with reproductive parameters. This study suggests that long-term circulating testosterone is associated with female reproduction in multiple ways. The possible trade-off between litter size and sex ratio may be mediated by testosterone and influenced by body fat and composition, which influence the individual's well-being. Exploring the multiple roles of testosterone in females may also help explain the complex relationship between obesity and reproduction.

Prohedonic Effect of Cannabidiol in a Rat Model of Depression.

BACKGROUND: Accumulating evidence suggests that cannabidiol (CBD) may be an effective and safe anxiolytic agent and potentially also an antidepressant. AIM: The objective of this study was to further examine these properties of CBD using the 'depressive-like' Wistar-Kyoto (WKY) rat, focusing on the drug's effect on anhedonia-like behaviors. METHODS: Forty-eight WKY and 48 control Wistar adult male rats were pretreated orally with CBD (15, 30 and 45 mg/kg) or vehicle. The saccharin preference test (SPT), the elevated plus maze (EPM) test and the novel object exploration (NOE) test were used. RESULTS: CBD showed a prohedonic effect on the WKY rats at 30 mg/kg in the SPT. In the NOE, CBD increased exploration of the novel object and locomotion at 45 mg/kg and increased locomotion at 15 mg/kg, indicating an improvement in the characteristically low motivation of WKY rats to explore. There was no similar effect at any dose in the EPM or in open-field behavior in the habituation to the NOE. CONCLUSIONS: These findings extend the limited knowledge on the antidepressant effect of CBD, now shown for the first time in a genetic animal model of depression. These results suggest that CBD may be beneficial for the treatment of clinical depression and other states with prominent anhedonia.