James R. Martin

Two-way avoidance and acute shock stress induced alterations of regional noradrenergic, dopaminergic and serotonergic activity in roman high- and low-avoidance rats

Various brain regions of male RHA/Verh and RLA/Verh rats were dissected out and deep-frozen immediately after 30 min in a shuttle box involving a) no shock (control), b) 40 inescapable shocks or c) 40 avoidable shocks. The RHA/Verh rats used in the c category exhibited about 80-85% learned avoidance. 5-HT, 5-HIAA, NA, MHPG-SO4, DA, DOPAC and HVA levels were subsequently measured in selected regions. NA levels were considerably reduced in the hypothalamus and pons/medulla of both selected lines of rats after acute shock stress, supporting the results of numerous studies which have indicated that NA turnover is nonspecifically increased by all types of stress, at least in those regions. An increase in cortical MHPG-SO4 and a reduction in hypothalamic 5-HT seen after avoidance learning also occurred after shock stress in RHA/Verh rats. Whereas RLA/Verh rats showed an increased metabolism of 5-HT in the hypothalamus and pons/medulla after shock stress, RHA/Verh rats showed the opposite response in the hypothalamus after the same treatment. A reduction in 5-HT metabolism was also evident in RHA/Verh rats, after avoidance learning, in the cortex, hippocampus and hypothalamus. These results indicated, pending further studies regarding, for example, possible genetic differences in tryptophan uptake and utilization, that 5-HT probably plays at least a modulatory role in the reaction to stress, and in avoidance behavior. That role may be either active or passive, depending upon the emotional status of the subjects. In regard to the DA responses measured in striatum and hypothalamus of the two rat lines, some divergent inter-treatment tendencies, as well as some similarities, were seen in DA metabolism in both regions, but almost none of the differences were significant.

Maze patrolling, open-field behavior and runway activity following experimental portacaval anastomosis in rats

Abstract Surgical construction of a portacaval shunt in patients with debilitating liver cirrhosis is frequently followed by the development of hepatic encephalopathy, characterized by severe cognitive and neuromuscular abnormalities. The rat with a portacaval anastomosis provides a heuristic animal model for the biochemical consequences of the portosystemic diversion of the circulation; the behavioral effects of such shunting were studied in the present investigation. The spontaneous behavior of male Sprague-Dawley rats with a chronic experimental portacaval anastomosis (end-to-side) was evaluated in a complex enclosed maze, an illuminated open field and an enclosed hexagonal runway. There was little evidence that portacaval shunted rats differed from sham operated rats in total activity, explored area, maze-center entry, or in either of two indexes of the efficiency of patrolling within a complex Dashiell-type maze over 13 successive days with three different maze configurations. Similarly, experimental and control rats did not differ in any of several responses assessed in an illuminated open field. However, rats with a portacaval shunt were hypoactive in a runway test given two months postsurgery. All experimental subjects were verified to have an open portacaval shunt and to have sustained significant liver atrophy. These results emphasize the subtle nature of the behavioral effects resulting from the surgical construction of a portacaval anastomosis in rats.

Dietary self-selection in cycling and neonatally ovariectomized rats.

Dietary self-selection patterns were assessed in normally cycling (four-day estrous cycle) rats with separate provisions of fat (olive oil), carbohydrate (sucrose), and protein (casein). There was no fluctuation in daily caloric intake across the estrous cycle, but animals did demonstrate changes in consumption of specific macronutrients during the 24-h period in which estrus occurred. At estrus, animals exhibited increased carbohydrate intake and decreased fat intake in comparison with the remaining three days of the cycle. There was also a somewhat decreased (non-significant) protein consumption at estrus. Rats that had been ovariectomized on day 5 postnatally and then tested as adults in our paradigm ingested approximately the same quantity of daily kilocalories as observed in intact animals; but ovariectomy produced changes in consumption of specific macronutrients. In comparison with the intact animals, ovariectomized animals displayed increased fat intake and decreased carbohydrate intake. Thus, the fat and carbohydrate self-selection patterns of our ovariectomized rats reflected the elimination of estrus behavior.

Drinking to intracellular dehydration following vagotomy in rats.

Abstract Abdominally vagotomized rats maintained on a solid diet drank less and had longer latencies to drink than sham vagotomized rats following IP injection of an osmotic load (0.75 M NaCl, 1% BW). However, these two groups did not differ in latency or water intake following injection of isotonic saline. Since both vagotomized and control rats drank more water and had shorter latencies following injection of hypertonic saline than after isotonic saline, vagotomy apparently attenuated but did not abolish osmotic drinking. Maintenance on a liquid diet and a brief fast prior to testing (to ensure an empty stomach) did not alter these results, indicating that the impairment of gastric emptying of solid food that accompanies total abdominal vagotomy cannot account for the attenuation of osmotically induced drinking. Furthermore, this deficit was seen even when intracellular dehydration was produced at different times during the circadian cycle and when water presentation was delayed 0.5 hr postinjection. In addition, vagotomized rats drank less than control rats following 16-hr water deprivation and exhibited a lower water-food ratio on ad lib regimen. However, vagotomized and sham vagotomized rats exhibited the same relative day-night difference in water consumption as well as short latency response to thermal pain, which with other results indicates that vagotomy did not result in a general impairment of behavior. These findings suggest that osmotic perturbations are detected by the viscera and the information conveyed to the brain via afferent vagus nerves.

Regional 5-HT analysis in roman high- and low-avoidance rats following MAO inhibition

5-HT and 5-HIAA levels were investigated in three brain regions of Roman high- and low-avoidance rats, following 10, 30 and 60 min of MAO inhibition (pargyline injection). Higher levels of 5-HT in the cortex at 30 and 60 min, as well as a higher disappearance rate of 5-HIAA in the midbrain/medulla region were exhibited by Roman high-avoidance rats, thus further characterizing the differences previously observed in whole brain 5-HT synthesis between these selected rat lines.

Exploratory behaviour of rats at oestrus.

Twenty-seven nulliparous RHA/Verh female rats received a daily-6-min test in a familial maze. The complex maze was of the Dashiell type and included a small illuminated central arena. It was demonstrated that these female rats more rapidly patrolled the maze at oestrus than on either of the two days preceding or following oestrus. Consistent with a number of earlier reports, it was also shown that general locomotor activity increased, body weight decreased, and the frequency of entry into the illuminated maze centre increased at oestrus.

Differential response to cholinergic stimulation in psychogenetically selected rat lines

Male and female rats of two lines psychogenetically selected for bipolar extremes in shuttle box avoidance were evaluated for tremor, salivation, chromodacryorrhea, and hypothermia following treatment with the muscarinic cholinergic agonist oxotremorine. Roman Low-Avoidance (RLA/Verh) rats exhibited more pronounced oxotremorine-induced tremor, chromodacryorrhea, and hypothermia than Roman High-Avoidance (RHA/Verh) rats. There was a sex difference only for the chromodacryorrhea response, with femles exhibiting a greater response following oxotremorine than males. In a subsequent experiment using female rats of both rat lines, it was demonstrated that pretreatment with the cholinergic antagonist scopolamine blocked oxotremorine-induced tremor, salivation and chromodacryorrhea responses in both rat lines and reduced the hypothermic effect observed in RLA/Verh rats (but not the much weaker hypothermia found in RHA/Verh rats) after oxotremorine injection. Pretreatment with the peripherally active cholinergic antagonist methscopolamine significantly reduced oxotremorine-induced salivation and chromodacryorrhea and somewhat decreased tremor and hypothermic responses in both rat lines. These results stand in contrast to the results of earlier research in which RHA/Verh rats exhibited greater behavioral depression in a tunnel maze than RLA/Verh rats following cholinergic manipulations. In view of evidence that these rat lines do not differ in number of muscarinic brain receptors, the present results may be due to genetic differences in other aspects of cholinergic neurotransmitter function, differences in the function of other neurochemical systems, or differences in the absorption, distribution, or metabolism of oxotremorine.

Alterations in ingestive behavior following experimental portacaval anastomosis in rats

Following surgical construction of an end-to-side portacaval shunt (PCS), male rats exhibited exaggerated consumption of glucose, saccharin, saline, and ethanol solutions relative to sham-operated rats in 24-hr preference tests with water present. Spontaneous daily water intake was also increased, but daily food intake and body weight were decreased by PCS. The overconsumption of glucose, saccharin, and saline exhibited by rats with portacaval shunts was reduced, or eliminated, by providing a corn supplement to their diet, consistent with the view that the disturbance of amino acid balance may have contributed to this ingestive abnormality. In a series of short drinking tests, rats with portacaval shunts consumed more of both 10% glucose and 10% fructose (given in separate tests) than sham-operated rats and glucose intake was greater than fructose intake for both of these groups. However, neither surgical nor saccharide condition affected the duration of the first bout or the initial inter-bout interval, indicating that the relative satiating properties of these two monosaccharides were probably not altered by portacaval shunting.

Schedule induced ethanol polydipsia in psychogenetically selected lines of rats

Schedule induced ethanol polydipsia was established in 28 male and female rats of two psychogenetically selected lines bred for extremes in active avoidance performance. These rats were maintained at 80% normal body weight and given 36 consecutive daily 45-min sessions with 3% (w/w) ethanol available. During the acquisition phase, food pellets were delivered intermittently on a FT-1 min schedule. Baseline tests preceded and followed the acquisition phase and involved presentation of 45 food pellets together at the start of a test. Roman High Avoidance (RHA/Verh) rats exhibited greater ethanol intake than Roman Low Avoidance (RLA/Verh) rats and female rats drank more ethanol (adjusted for body weight differences) than male rats during baseline and acquisition phases. Furthermore, baseline ethanol intake increased significantly from the initial block to the final block of sessions following acquisition testing, but remained significantly lower than ethanol intake during the final block of acquisition tests. In a second experiment, naive female rats of the two psychogenetic lines were given baseline tests or sessions with food intermittently delivered on a FT-2 min schedule following a period of free feeding or a 20-hr session 3% ethanol was continuously available. In the initial phase of acquisition, fasted RHA/Verh rats drank more ethanol than RLA/Verh rats. In the second phase, undeprived rats of these two lines did not differ in ethanol intake. In a final acquisition phase, fasted RHA/Verh and RLA/Verh rats did not differ significantly in ethanol consumption. Under both deprivation regimens, baseline ethanol intake increased from the initial to the final baseline test. The ethanol consumption of fasted rats in the final acquisition test was significantly greater than that in the final baseline test. Thus, although pronounced and relatively enduring differences in the schedule induced ethanol intake of these two rat lines were observed under the condition of chronically reduced body weight, this strain difference was relatively weak and observed only in the initial phase of acquisition when 20-hr fasted rats were tested.

Exaggerated consumption of saccharide solutions following experimental portacaval anastomosis in rats.

Male Sprague-Dawley rats were subjected to end-to-side portacaval anastomosis and permitted to recover from the acute effects of this surgical procedure. Subsequently, portacaval-shunted rats consistently drank abnormally large quantities of 5% (W/V) solutions of glucose, fructose, and sucrose in 24-hr two-bottle tests with water present as the second fluid. The volume of glucose consumed was not altered when the concentration was increased from 5 to 10%. The pattern of preferences exhibited by the portacaval-shunted rats was similar to that of the sham-operated rats, even in three- to five-choice preference tests with several palatable fluids available simultaneously. However, no abnormally high consumption of either water- or quinine-adulterated sucrose solution was noted. Although exaggerated consumption of 0.1% sodium saccharin was not observed in the present study, subsequent unpublished research indicates that when portacaval-shunted rats are given a 0.06% sodium saccharin solution in a preference test, overconsumption relative to control rats occurs. Portacaval shunts were verified both by anatomical examination and by determination of hepatic and testicular atrophy at the conclusion of the investigation. The evidence suggests that over-responsiveness to a palatable taste underlies this phenomenon of exaggerated saccharide consumption.