Mitra A, Alvers KM, Crump EM, Rowland NE. Effect of high-fat diet during gestation, lactation, or postweaning on physiological and behavioral indexes in borderline hypertensive rats. Am J Physiol Regul Integr Comp Physiol 296: R20 -R28, 2009. First published October 29, 2008 doi:10.1152/ajpregu.90553.2008.-Maternal obesity is becoming more prevalent. We used borderline hypertensive rats (BHR) to investigate whether a high-fat diet at different stages of development has adverse programming consequences on metabolic parameters and blood pressure. Wistar dams were fed a high-or low-fat diet for 6 wk before mating with spontaneously hypertensive males and during the ensuing pregnancy. At birth, litters were fostered to a dam from the same diet group as during gestation or to the alternate diet condition. Female offspring were weaned on either control or "junk food" diets until about 6 mo of age. Rats fed the high-fat junk food diet were hyperphagic relative to their chow-fed controls. The junk food-fed rats were significantly heavier and had greater fat pad mass than those rats maintained on chow alone. Importantly, those rats suckled by high-fat dams had heavier fat pads than those suckled by control diet dams. Fasting serum leptin and insulin levels differed as a function of the gestational, lactational, and postweaning diet histories. Rats gestated in, or suckled by high-fat dams, or maintained on the junk food diet were hyperleptinemic compared with their respective controls. Indirect blood pressure did not differ as a function of postweaning diet, but rats gestated in the high-fat dams had lower mean arterial blood pressures than those gestated in the control diet dams. The postweaning dietary history affected food-motivated behavior; junk food-fed rats earned less food pellets on fixed (FR) and progressive (PR) ratio cost schedules than chow-fed controls. In conclusion, the effects of maternal high-fat diet during gestation or lactation were mostly small and transient. The postweaning effects of junk food diet were evident on the majority of the parameters measured, including body weight, fat pad mass, serum leptin and insulin levels, and operant performance. developmental programming; blood pressure; metabolic syndrome; motivation and Nutrition Examination Survey (NHANES III) found that Ͼ50% of nonpregnant women of child-bearing age (20 -39 yr of age) in the United States of America were overweight or obese (body mass index Ͼ25 kg/m 2 ), and Ͼ30% of girls between the ages of 12-19 were either at risk of being overweight or were overweight (22). These statistics imply that almost half of all babies are born to mothers who are either overweight or obese during pregnancy, and this fraction is likely to increase in the future.Adverse effects of obesity on mothers have been wellstudied; these include gestational diabetes, preeclampsia, prolonged delivery, and delayed wound healing postdelivery, all of which significantly increase health care costs (18). Babies born to obese women have a higher incidence of cong...

Despite the efficacy and widespread use of methylphenidate (MPH) as a treatment for Attention Deficit Hyperactivity Disorder (ADHD), clinical and preclinical findings indicate it has abuse potential. Environmental enrichment reduces susceptibility to cocaine and amphetamine self-administration, and decreases impulsive behavior, but its effects on MPH self-administration are unknown. The present experiments sought to determine the influence of environmental enrichment on MPH self-administration. Male rats were raised in an enriched condition (EC) or isolated condition (IC). They were trained to self-administer MPH (0.3 mg/kg/infusion) and then exposed to varying doses of MPH on either a fixed ratio (FR; Experiment 1) or progressive ratio (PR; Experiment 2) schedule of reinforcement. EC rats earned significantly fewer infusions of MPH at low doses (0.03 and 0.056 mg/kg/infusion) than IC rats under both schedules; however, no differences were observed at high unit doses (0.1–1.0 mg/kg/infusion). During saline substitution at the end of MPH self-administration, EC rats also responded less for saline than IC rats, indicative of more rapid extinction. As with other stimulant drugs with different mechanisms of action, environmental enrichment during development protects against self-administration of MPH at low unit doses, but not at high unit doses.

Rationale The vesicular monoamine transporter 2 (VMAT2) has been identified as a potential target for the treatment of methamphetamine (METH) abuse. GZ-793A is a potent and selective VMAT2 inhibitor that has been shown to block the primary and conditioned rewarding effects of METH, while demonstrating no abuse liability when given alone. Objectives The aim of the current study was to determine if GZ-793A attenuates METH- or cue-induced reinstatement of METH-seeking after a period of extinction. The effect of acute GZ-793A on locomotor activity also was assessed. Methods After a period of extinction, rats were administered GZ-793A (15 mg/kg, s.c.) 15 min prior to a priming injection of METH or re-exposure to cues associated with METH infusions. GZ-793A also was administered 20 min prior to an injection of METH (0.5 mg/kg, s.c.) or saline to determine its effect on locomotor behavior. Results Pretreatment with GZ-793A (15 mg/kg) decreased cue-induced reinstatement, without demonstrating any response suppressive effects when administered in the absence of reinstating stimuli. GZ-793A also decreased methamphetamine-induced reinstatement; however, response suppressant effects of GZ-793A were obtained when the compound was presented alone. In this latter experiment, GZ-793A may have reduced responding for the conditioned reinforcing effects of the contingently available cues rather than having non-specific effects on baseline responding. GZ-793A had no effect on locomotor activity when administered alone or with METH. Conclusions GZ-793A and related VMAT2 inhibitors may be promising leads for reducing the risk of relapse to METH use following exposure to drug-associated cues.

Stress in combination with genetic susceptibility is a factor in the development of hypertension. We used borderline hypertensive rats to investigate whether exposure to high-fat and/or junk-food diet at different stages of ontogeny has programing consequences on stress responses. Wistar dams were fed a high- or low-fat diet for 6 weeks prior to mating with spontaneously hypertensive males, and during gestation. At birth, litters were fostered either to a dam in the same or an alternative diet condition as during gestation. After weaning, male offspring were fed either a control-chow diet or an intermittent junk food fatty diet. Between postnatal days 57-61, half of the rats in each dietary group received daily social defeat sessions using a resident-intruder protocol, and the other half were unstressed controls. Blood pressure was measured indirectly both before and after each defeat session. On the final day, rats were killed for physiological measures. Socially defeated rats showed large increases in serum corticosterone concentration and adrenal hypertrophy, indicating the effectiveness of this non-adapting stressor. Serum corticosterone level was also higher in rats fed with the junk-food diet post-weaning compared with those fed with chow only, but there were no significant effects of gestational or lactational dietary history.

The purpose of this study is to determine whether maternal over‐nutrition contributes to obesity, hypertension, and altered glucose handling in rats with a genetic predisposition to mild hypertension. Adult female Wistar rats were maintained on either a high‐fat (HF: 60% lard) or low fat (LF: 10%) diet for approximately 8 weeks, after which they were mated with male spontaneously hypertensive rats (SHR) to yield BHR offspring. Gestating females were maintained on the same diets as prior to impregnation. At parturition, the litters were culled and cross‐fostered either to a dam with either low or high fat diet, so yielding 4 groups for the period of lactation: HF/HF, LF/LF, HF/LF, LF/HF. At weaning, half the females from the litters were fed Purina chow while the other half were placed on a varied HF cafeteria diet for the entire duration of the experiments. At PD 160 we obtained indirect blood pressure measurements, at PD 200 the rats were fasted for 18 hours and then an oral glucose‐tolerance test was administered. At this point, the rats were then placed in an operant paradigm to examine for differences in motivation to obtain a palatable food, given the differences in their prenatal and diet histories. These studies are currently under way; preliminary results suggest rats on the high‐fat diets have reduced glucose tolerance and are significantly heavier than their chow‐fed counterparts. Research supported NIH‐DK064712.