BORER, K. T., R. BONNA AND M. KIELB. Hippocampal serotonin mediates hypoactivity in dietarily obese hamsters:A possible manifestation of aging? PHARMACOL BIOCHEM BEHAV 31(4) [885][886][887][888][889][890][891][892] 1988.--To determine whether endogenous opiates mediate hyperactivity in food restricted hamsters and serotonergic fibers innervating the hippocampus mediate hypoactivity in obese hamsters, food restriction and high-fat diet supplementation were used to produce significant body fat changes (8 vs. 21%). The levels and pattern of spontaneous running were examined after IP saline or naloxone HC1 (20 mg/kg) and following the infusion of vehicle and 5,7-dihydroxytryptamine creatine sulfate (4/~g/2/zl) into rostromedial septum of mature female hamsters. Septum-medial preoptic area (POA), hippocampus, hypothalamus, and cortex were dissected from the three groups as well as from two additional groups of hamsters receiving vehicle or neurotoxin. Concentrations of serotonin, norepinephrine, and dopamine were measured in these tissues by HPLC method. Fat-fed hamsters were hypoactive relative to food-restricted hamsters. Naloxone had no significant effect on running behavior. Serotonin neurotoxin increased the running activity of fat-fed hamsters to the level displayed by control hamsters by increasing the number of runs, the total activity level, the speed of running and by decreasing the duration of pause:~. Neurotoxin led to selective deletion of serotonin in the hippocampus (77~) and parietal cortex (50%). Serotonergic fiber~ innervating the hippocampus thus appear to mediate the hypoactivity that is induced by dietary obesity iv. mature hamsters. Since serotonin mediates some other manifestations of aging, and slow weight increases characterize mid-portion of hamster life span, we hypothesize that serotonergic mediation of hypoactivity is another manifestation of aging.
FastingHyperactivity Naloxone Limbic forebrain MECHANISMS which regulate body energy balance and control spontaneous running behavior are interrelated. This is apparent at the time of sexual maturation in rodents when there is a rapid increase in spontaneous running activity to an all-time high at the same time as the rate of somatic growth and of weight gain rapidly decline (8). It is also evident after the onset of sexual maturity, during the period of slow weight gain when activity levels decline in inverse proportion to increases in body size (4,8,37). Thus, when the weight of mature hamsters doubles, their spontaneous activity levels are reduced by about 50% (4,8). Furthermore, when accumulation of excess energy results in obesity, mice (45), rats (37,40), and hamsters (5) display even greater spontaneous hypoactivity.Reciprocal relationship between energy regulation and spontaneous running remains intact after some neurosurgical manipulations which affect both mechanisms. In the hamster, voluntary running levels are reduced by 80% following electrocoagulative lesions of rostromedial septum (10), horizontal transection of septo-hippocam...