Robert J. Waldbillig

The role of the dorsal and median raphe in the inhibition of muricide

Previous work has implicated the putative neurotransmitter serotonin in the inhibition of muricide. This study examined the possibility that the nuclei of the mesencephalic raphe function differentially in the control of this behavior. The results indicate that radiofrequency lesions confined to the dorsal raphe are sufficient to produce muricide in naturally non-killing rats. Lesions of the median raphe do not produce attack. Evidence is presented that suggests that the region of the tegmentum juxtaposed to the dorsal raphe and central gray contains neural mechanisms necessary for the final behavioral components of the attack sequence.

Hormones and hedonics cholecystokinin and taste: A possible behavioral mechanism of action

Abstract Both water deprived and non-deprived rats were used to study the mechanism of cholecystokinins (CCK) suppressive effect on food intake. Evidence is presented indicating that CCK may produce its effect on food intake by modulating the behavior-controlling characteristics of taste. Specifically, it was found that in ad lib rats the synthetic octapeptide of cholecystokinin (CCK-8) suppressed sucrose intake during the first few (1–3) min of a drinking test without influencing the drinking latency. Because in these conditions the ingestive behavior is maintained primarily by the sucrose taste, these findings are taken to indicate that the CCK-8 induced suppression of intake is due to a reduction in the behavior-maintaining characteristics of that taste. It was also found that the presence of a sucrose taste was a necessary and sufficient condition to allow CCK-8 to suppress intake of water by water-deprived rats. The enabling effect of sucrose is not related to its metabolic impact because the CCK-8 induced suppression occurs before sucrose can be absorbed from the gastrointestinal tract. In contrast to earlier work, it was found that while food and water deprivation are not necessary preconditions for a CCK-8 induced suppression of intake, these conditions do modulate the magnitude of the CCK-8 effect. To the extent that these findings can be related to the taste characteristics of the drinking solutions and not to some correlated variable (e.g. osmolality), these results have relevance for the alliesthesia literature where physiological manipulations are reported to alter the “hedonics” associated with food.

The role of electrically excitable mesencephalic behavioral mechanisms in naturally occurring attack and ingestive behavior

Abstract Electrical stimulation of the mesencephalon dorsolateral to the central gray has been shown to elicit mouse killing but not ingestive behavior. In contrast, stimulation of the ventrolateral portions of the mesencephalon elicits ingestive but not mouse killing behavior. The present experiment investigated the effects of radiofrequency lesions of these areas on naturally occurring muricide and eating. The results indicate that the areas originally outlined with electrical stimulation play a role in the naturally occurring forms of these behaviors and that at the level of the mesencephalon these mechanisms are anatomically partially segregated.

Dietary self-selection in intact, ovariectomized, and estradiol-treated female rats

The effects of estrogenic stimulation on diet selection were examined in intact, estrous cycling rats, ovariectomized (OVX) rats, and OVX rats given estradiol benzoate (EB) hormone replacement therapy. In Experiment 1, OVX was associated with the nearly exclusive choice of the more calorically dense diet of a pair of diets varying in the concentration of one of the three basic macronutrients (i.e., fat, carbohydrate, and protein), an effect that was decreased by EB administration. In the second experiment, dietary self-selection was examined in intact, estrous cycling rats given access to an isocaloric diet triplet of fat, carbohydrate (CHO), and protein. Total caloric intake and body weight did not vary across the estrous cycle. However, diet selection did vary. Fat intake increased; CHO and, to a lesser extent, protein intake decreased during estrus. An opposite diet selection occurred during diestrus. In Experiment 3, OVX resulted in progressive increases in CHO and protein intake, with a concurrent decrease in fat consumption. The EB treatment partially reversed this diet selection profile (Experiment 4). These results were confirmed by diet pairs with both naturally occurring and experimentally produced estrogenic stimulation (Experiments 5 and 6). These data are consistent with the findings of previous research demonstrating estrogenic reduction in CHO intake with standard high-CHO commercial diets. In addition, an increase in fat intake during estrogenic stimulation was found.

The suppression of sucrose intake by cholecystokinin is scaled according to the magnitude of the orosensory control over feeding

The intestinal hormone cholecystokinin (CCK) has been shown to play a role in the termination of food intake, however its behavioral mechanism of action remains to be determined. Recent work from this laboratory suggested that the suppression of intake with CCK is dependent upon the specific orosensory characteristics of the substance being consumed and that the hormone may suppress intake by altering the behavior maintaining characteristics of orosensory stimuli. The present study further investigated this suggestion by determining whether changes in the orosensory characteristics of food after the magnitude of the suppressive effect of CCK. Specifically, the magnitude of the CCK effect on the intake of sucrose solutions of various concentrations was determined on non-deprived rats. The results of this work indicate that the suppressive effect of synthetic CCK (CCK-8) cannot be overridden by increases in sucrose concentration. In contrast, it was found that over a range of sucrose concentrations, the magnitude of the CCK effect increased with solution concentration. Because sucrose concentration predicts both caloric density and the magnitude of orosensory control (as measured by grams consumed), it appears that CCK may act on this control to regulate meal size in proportion to the caloric density of the food.

Suppressive effects of intraperitoneal and intraventricular injections of nicotine on muricide and shock-induced attack on conspecifics ☆

Rats were used to investigate the effect of nicotine on mouse-killing and foot shock-induced attack on conspecifics. It was found that intraperitoneal injections of nicotine (100-1000 micrograms/kg) suppressed mouse-killing in a dose dependent manner. The suppression of mouse-killing by nicotine was not blocked by hexamethonium (30 mg/kg), a peripheral nicotinic receptor blocking agent. Mecamylamine (30 mg/kg), a nicotinic blocking agent with central effects, did reduce the inhibition of attack produced by nicotine. Both intraperitoneal and intraventricular injections of nicotine suppressed shock-induced attack on conspecifics. Shock-elicited flinch, vocalization, and escape were not influenced by nicotine injections. These findings give further support to the view that muscarinic and nicotinic compounds produce antagonistic effects on certain types of attack behavior.

Oroesophageal factors in the patterning of drinking

Abstract Eleven albino rats were fitted with chronic gastric fistulas to determine the effect of stomach draining on the pattern of drinking. Each animal was given ten two-hr drinking tests with the gastric fistula open on every other test. On the first open fistula test intake was five times greater than that of the following closed fistula test. However, the first fistula opening did not alter the temporal position of the first pause in intake. Across subsequent open, but not closed fistula tests, consumption increased further so that on the last test open fistula intake was ten times greater than in closed fistula intake. On the basis of these results it is suggested that the early portion of the drinking sequence is under the control of conditioned oroesophageal stimuli while the later phases of the sequence are controlled by stimuli arising from the alimentary canal and/or blood.

Insulin-induced drinking: An analysis of hydrational variables

Abstract Male Long-Evans rats were used to study the effects of insulin on plasma volume, plasma osmolality and water intake. It was found that intraperitoneal injections of insulin elicited drinking in the absence of food. The insulin-induced drinking (IID) was dose-dependent and was not accompanied by either plasma hypovolemia or hyperosmolality, conditions traditionally known to produce increased water intake. Instead, the onset of drinking was associated with the reverse conditions, a state of absolute plasma hypervolemia and hypo-osmolality. Despite the absolute hypervolemia, insulin produced an efflux of water from the vasculature. In general, the magnitude of the IID appeared to be related to the magnitude of this efflux. It was also found that the plasma volume of these animals was controlled by two opposing processes: a handling-induced hypervolemia and an insulin-induced efflux of vascular water. Plasma osmolality also appears to be controlled by opposing processes: a hypo-osmolality related to an insulin-induced hypoglycemia and an adrenal medullary restoration of plasma osmolality despite the continuing loss of vascular glucose. Because the magnitude of the IID was related to the magnitude of the insulin-induced decrease in plasma volume and not the absolute level of plasma volume, it appears that under these conditions, drinking is controlled by the directional flux of vascular water.

Disproportionate increases in locomotor activity in response to hormonal and photic stimuli following regional neurochemical depletions of serotonin

The role of forebrain serotonin in behavior-related energy output was assessed in two locomotor activity tests conducted 3 and 6 months after bilateral, intrahypothalamic microinfusion of the serotonin neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT). The serotonin-depleted animals exhibited a long-lasting and stable increase in energy expenditure as locomotor activity. This increased activity was investigated at the behavioral level by relating the hyperactivity to estrous cycle, photoperiod and body weight. Although the serotonin depletion-induced hyperactivity occurred in all photoperiod and estrous cycle stages, its magnitude was disproportionately increased during light and estrus. This hyperactivity could not be related to decreases in body weight because the serotonin-depleted animals weighed significantly more than the control animals. These animals responded to the weight loss that normally accompanies wheel running by increasing their activity to the same proportion as the other groups. The neuroanatomical and neurochemical substrate of the increased locomotor activity was investigated with a regional neurochemical assay for serotonin, dopamine and norepinephrine. This assay revealed that the toxin had no effect on dopamine or norepinephrine in any structure analyzed; however, serotonin was depleted in the hippocampus, septum and, to a lesser degree, in the hypothalamus. Serotonin levels were negatively correlated with overall activity. The magnitude of the disproportionate increase in activity during light and estrus was negatively correlated with hippocampal serotonin level. These results indicate that forebrain depletions of serotonin differentially affect the control of activity exerted by the phases of the photoperiod and estrous cycle. However, the modulation of activity levels by decreases in body weight remains intact.

Rostral hypothalamic microinfusions of 5,7 dihydroxytryptamine produce anatomically and neurochemically selective depletions of hippocampal serotonin and increase the influence of estrogen and food deprivation on locomotor activity

Ovariectomized Long-Evans rats received bilateral rostral hypothalamic infusions of 5,7-dihydroxytryptamine (5,7-DHT). Neurochemical determination of catecholamines (CA) and indoleamines in the hippocampus, hypothalamus and mesencephalon revealed that 5,7-DHT infusions had no effect on CA content in these areas nor in mesencephalic serotonin or 5-hydroxyindoleacetic acid (5-HIAA). However, the neurotoxin produced significant decreases in hippocampal serotonin and 5-HIAA. Serotonin-depleted animals exhibited an increase in both spontaneous and estradiol-induced wheel running. In addition it was found that serotonin-depleted animals exhibit an enhanced activity response to starvation. Because estrogen is thought to decrease serotonergic transmission, the enhanced activity response to estrogen may be secondary to an estrogen-related exaggeration of the 5,7-DHT-induced serotonin depletion. The increased activity effect of starvation may indicate that serotonin-depleted animals do not effectively mobilize energy stored as lipid.