The impact of antipsychotic drugs on food intake and body weight and on leptin levels in blood and hypothalamic ob-r leptin receptor expression in wistar rats

Abstract

OBJECTIVES:The aim of our study was to investigate the impact of typical and atypical antipsychotic drugs on leptin concentration in blood and changes in the receptor expression in the hypothalamus of male Wistar rats.METHODS:From the age of 13 to 18 weeks, three groups of 20 animals were fed an average dose of 3.5 ± 0.03 mg/ kg body weight (BW) haloperidol; 30.6 ± 0.22 mg/kg BW clozapine; or 14.9 ± 0.13 mg/kg BW ziprasidone in ground food pellets containing 15% fat. Twenty control animals received no drugs. Blood samples were taken at week 14, 16, and 19. Locomotor activity and exploratory behavior were measured using the alcove test at weeks 15 and 17. The expression of the hypothalamic leptin receptor in rat brains was determined by using a Western blot.RESULTS:Rats medicated with haloperidol and ziprasidone showed a significantly decreased percentage weight gain and food consumption. We observed no differences in the alcove test, but locomotor activity was significantly reduced in the haloperidol group. Except for rats in the clozapine and ziprasidone groups, after 2 weeks of drug application, we found no changes in the leptin blood concentrations among the four groups or animals within each group. Moreover, we did not find specific differences in hypothalamic leptin receptor expression among the groups.CONCLUSION:We concluded that in male Wistar rats during this treatment period, the tested drugs did not act directly on the leptin regulatory system. We recommend further studies using long-term treatment of different rat strains.

Time-dependent effects of haloperidol on glutamine and GABA homeostasis and astrocyte activity in the rat brain

“…Central leptin injection in wild-type mice decreased food intake and this effect was magnified by haloperidol (Kim et al 2010). Although 6 weeks of oral haloperidol did not alter leptin levels or hypothalamic leptin receptor expression in rats (Minet-Ringuet et al 2005; von Wilmsdorff et al 2010), 6 months of haloperidol administration in the current study might have modulated the activity of leptin by blocking D2 receptors in the hypothalamus, producing an anorectic effect.…”

Atypical antipsychotics and effects on feeding: from mice to men

“…Its predominant D 2 blockade represents a property shared by all APs and the foundation for therapeutic efficacy in psychosis. Treatment of rodents with HAL produces variable effects on total food intake and, in general, higher doses have been shown to inhibit feeding (von Wilmsdorff et al 2010), likely in part related to motor-related side effects (Hartfield et al 2006;Zhang et al 2005). Interestingly, HAL has been shown to decrease the hedonic value of food (Galistu et al 2011;Hartfield et al 2003) but can also decrease satiety at a lower dosing range (Lee and Clifton 2012;Kaur and Kulkarni 2002).…”

“…Antelman et al (1977) acutely administered CLO either directly into the brain (0.04-50 μg) or via gavage (10-20 mg/kg) and found dose-dependent increases in food intake regardless of route of administration. However, the majority of remaining studies investigating the effect of CLO showed no significant changes or even decreases in cumulative food intake and body weight in both male (Baptista et al 1993;Choi et al 2007;Galistu et al 2011;von Wilmsdorff et al 2010) and female rats (Albaugh et al 2006;Baptista et al 1993;Choi et al 2007;Cooper et al 2008a). One potential explanation for this discrepancy is the solubility constraints of chronic CLO administration; the desired drug concentration cannot be maintained in mini-pumps to allow delivery of therapeutic doses (Choi et al 2007;Kapur et al 2003).…”

“…Studies in rodents have consistently failed to demonstrate increased food intake following ZIP treatment (Fell et al 2005a;Fell et al 2007;Fell et al 2008;Hartfield et al 2006;Kirk et al 2004;MinetRinguet et al 2006a;Park et al 2012;Shobo et al 2011b;Snigdha et al 2008;von Wilmsdorff et al 2010). Negative findings occur regardless of sex, method of drug administration, time of drug administration relative to outcome measured, or dose range.…”

Effects of ziprasidone and olanzapine on body composition and metabolic parameters: an open-label comparative pilot study

“…To date, increased appetite, sedation, and hyperprolactinemia have all been associated with antipsychotic-induced weight gain [21-24]. However, their precise mechanism has yet to be elucidated.…”