Lori M. Dixon

Effects of dietary fat on pain threshold, thermoregulation and motor activity in rats.

Groups of young male Sprague-Dawley (albino) or Long-Evans (hooded) rats were fed the same semi-purified diets containing 20% (w/w) fat in the form of soybean oil vs. lard, or a reference diet of standard Purina Chow (4.5% mixed fats) for 21 days. Behavioral testing after this time revealed that albino rats fed the diet containing soybean oil had increased paw-lick latencies on a 58 degrees C hot plate compared to chow-fed rats. In addition, both strains fed the diet containing soybean oil were protected from hypothermia induced by placing animals in a 4 degrees C cold room for 60 min following systemic injection of 10-15 mg/kg d-amphetamine. Rats of both strains fed the lard diet displayed paw-lick latencies similar to those shown by rats fed chow and hypothermic changes intermediary to those shown by rats fed soybean oil vs. chow diets. Horizontal crossings as well as rearings in a 15 min test of open field activity were the same for all diet groups within strains. No substantial differences were observed in the number of calories consumed, amount of body weight gained or basal colonic temperatures across diet conditions. The results suggest that a soybean oil-based diet can alter physiological mechanisms which mediate these indices of pain perception and thermoregulation. More generally, they indicate that qualitative changes in dietary fat content may be capable of altering certain behavioral states.

Learning is improved by a soybean oil diet in rats

A semi-synthetic diet containing 20% polyunsaturated fat (soybean) oil was fed to young male hooded rats for 21 days. These animals exhibited improved performance on an environmentally-cued testing paradigm which is thought to reflect cognitive learning skills (i.e., Place Navigation Water Task). Other rats fed the same base diet but containing 20% saturated fat (lard) showed no such improvement compared to chow-fed (4.5% mixed fat) controls. The animals fed soybean oil also exhibited a transient resistance to extinguish this learning. This improved learning could not be explained by changes in general motor activity, basal body temperature, energy consumption, body weight, or in the brain activity of choline acetyltransferase, the marker enzyme for cholinergic neurons. These findings constitute the first evidence that short-term variations in the quality of dietary fat can enhance mammalian learning.

Effects of chronic haloperidol on stress-induced oral behaviour in rats.

Rats received daily injections of haloperidol (HAL, 5 mg/kg SC, or IP) or tartaric acid vehicle for 14–21 days. Four to six days after discontinuation of the daily injections, rats were given a single 5-min tail pinch (TP) test. HAL-treated rats showed significantly shorter latencies to display oral behaviours (OB: licking, gnawing, or drinking) compared to controls in five separate replications. Food consumption per se was not consistently affected. Shorter OB latencies were significantly corrlated both with increased striatal 3H-spiperone binding and with apomorphine stereotypy scores. In a final eperiment, this effect of HAL on OB latencies was blocked by a systemic injection of naloxone (2 mg/kg IP) prior to the TP test. Naloxone did not affect OB latency in control rats, suggesting the possibility of endogenous opiate involvement in the chronic HAL effects. The overall results suggest that OB latencies following mildly activating stimulation may provide a useful behavioural assay for neuroleptic-induced oral abnormalities as well as a functional index of striatal dopamine D-2 receptor sensitivity.

Graded increases in brain GABA: differential effects on feeding and other behaviours in rats.

Elevations of brain gamma-aminobutyric acid (GABA) induced by inhibitors of GABA transaminase (GABA-T) are known to induce a number of functional effects including depression of food intake. The aim of the present study was to determine the brain GABA elevation threshold for changes in feeding and several other behaviours, in an effort to clarify whether feeding changes might be secondary to other functional deficits. To this end, various doses of the GABA-T inhibitors ethanolamine-o-sulfate (EOS) and gamma-vinyl GABA (GVG) were injected intracisternally and effects on whole brain GABA, food and water intake, open field activity, catalepsy indices, pain sensitivity, and core temperature were assessed 24 h later. Progressive increases in brain GABA levels were found to differentially affect the responses studied. At the low end of the continuum, significant decreases in feeding behaviour were associated with relatively modest increases in brain GABA (40-60%). At higher levels of GABA elevation (greater than 100%), changes in motoric functions and rectal temperature became apparent. At still higher levels (greater than 200% increases in brain GABA), significant antinociceptive effects were detected. These results support the notion that feeding decreases induced by low doses of GABA-T inhibitors may reflect a fairly specific effect on appetite mechanisms, but also indicate that with increasingly higher doses several other deficits are likely to contribute to the overall decrease in food intake.

Desipramine reduces plasma but not brain thyroxine levels.

There is a well known association between abnormalities of thyroid function and affective illness (Joffe et al 1984). A variety of abnormalities of thyroid hormone levels have been reported in patients with major depression, including blunted thyrotropin response to thyrotropin releasing hormone (Loosen 1985) and alterations in circulating thyroxine (T4) and triiodothyronine (T3) (Gold et al 1981; Joffe et al 1985). A consistent finding observed in depressed patients is that treatment with a variety of antidepressants is associated with significant but limited decreases in circulating thyroid hormone levels, particularly T4 (reviewed in Bauer and Whybrow 1988). Furthermore, in two of these studies, responders to tricyclic antidepressant treatment had significantly greater reductions in circulating T4 and free T4 as compared with nonresponders (Baumgartner et al 1988; Joffe and Singer 1990). These findings have led us to hypothesize that reductions in brain T4 are required for antidepressant response (Joffe et al 1984). Although response to antidepressants may be associated with significant changes in circulating thyroid hormone levels, the direct effect of tricyclic antidepressants on brain thyroid hormone levels have not, to our knowledge, been directly evaluated. In this study, therefore, we compared the effects of chronic desipramine treatment on levels of T3 and T4 in the plasma and brain of the rat.

Cerebellar glutamate metabolizing enzymes in spinocerebellar ataxia type I

We measured the levels of three glutamate metabolizing enzymes, namely, glutamate dehydrogenase (GDH), aspartate aminotransferase (AAT), and glutamine synthetase (GS) in cerebellar and occipital cortices of nine patients with dominantly-inherited olivopontocerebellar atrophy (OPCA; spinocerebellar ataxia type I). As compared with the controls, mean GDH activities in cerebellar cortex of the OPCA patients were normal whereas levels of AAT (−17%) and the glial enzyme GS (−27%) were significantly reduced. No statistically significant changes were observed in occipital cortex, a morphologically unaffected brain area. We suggest that the decreased GS levels could reflect impaired capacity of astrocytes to metabolize glutamate which might contribute to the degenerative processes in OPCA cerebellum.

Brain cytochrome oxidase activity after kindled seizures : a quantitative histochemical mapping study

Quantitative histochemistry was used to analyze changes in cytochrome oxidase (CO) activity in 93 brain regions after entorhinal cortex kindling. Rats were kindled to at least six stage-5 seizures and sacrificed either 24 h or 28 days after the last convulsion. Regional brain CO activity was quantitated in histological sections using calibrated densitometric standards. No statistically significant differences in regional CO activity between kindled and control brains were seen either 24 h or 28 days after the last convulsion. These results suggest that the brain changes underlying the kindling state are not reflected in localized alterations in mitochondrial respiratory capacity. They also indicate that long-lasting changes in regional brain CO activity recently found after electroconvulsive shock are not common to all types of seizures.

Regional thyroid hormone levels in rat brain

Levels of T4 and T3 were measured in half-brain and seven brain regions. Although thyroid hormones were distributed throughout the brain, T4 levels were highest in cerebellum and thalamus. The highest T3 levels were observed in the thalamus and lowest levels were found in olfactory bulb, hypothalamus, and amygdala.