William J. Freed

Effects of acute and chronic ethanol intake on synaptosomal glutamate binding activity

Abstract The effects of acute and chronic ethanol administration in vivo, on brain synaptosomal glutamate binding activity were explored. In the l -glutamic acid concentration range in which high affinity stereospecific binding to synaptic membranes takes place, both acute and chronic ethanol administration led to progressively greater glutamate binding depending on the chronicity of exposure to ethanol (2 hr to 16 days). These changes appeared to be primarily due to an increase in the maximum binding capacity of these membrane binding sites rather than to changes in their affinity towards the ligand. The withdrawal from ethanol following 16 days of continuous exposure brought about a slow reversal of the increased glutamate-binding activity over a period of 6 days. A brief (2 hr) exposure to ethanol in vitro, produced a small decrease in glutamate binding, whereas prolonged exposure to the alcohol during equilibrium dialysis had a biphasic effect on ligand binding to synaptosomal membranes. These results are suggestive of a possible role for l -glutamic acid in the nervous system during ethanolism and the post-withdrawal reaction.

Do rats terminate hypothalamic stimulation only in order to turn it on again

Rats will operate a shuttle box to both initiate and terminate electrical stimulation in the hypothalamus (ESH). Some believe that they terminate the ESH because it changes from rewarding to punishing if left on for more than a few seconds. Others believe that while the onset of ESH is rewarding, its reward strength rapidly diminishes and they terminate it only in order to turn it on again. If so, rats given only one opportunity each session to initiate and terminate the ESH should not terminate it, because they cannot turn it on again during the session. But in the present experiment it was found that they do terminate it, thus supporting the punishment hypothesis.

The role of nerve-growth factor (NGF) in the central nervous system

NGF is a protein that stimulates growth and differentiation of sympathetic and sensory components of the peripheral nervous system. The purpose of this review is to examine the evidence that NGF has similar activity in the central nervous system. First, the primary mode of interaction of NGF with the nerve cell will be discussed, and the possibility that such an interaction takes place in the brain will be examined. Recent studies have demonstrated that NGF promotes regenerative sprouting of damaged catecholamine-containing neurons in the brain. The next part of the paper reviews this literature, and other findings that indicate or contraindicate a role of NGF in brain maturation of maintenance. The final part of this paper suggests specific avenues for future research in this area, and presents conclusions regarding the literatureon brain activity of NGF to date.

Effects of water temperature on the reward value and satiating capacity of water in water-deprived rats

Since orolingual cooling is a primary reward for water-deprived rats, cold water should be more rewarding than warm water. Hooded rats were allowed to bar press on a VI 1-min schedule for water at approximately 12° or 36°C. Testing started when their body weights had dropped to 80% of their predeprivation levels and was continued as their weights were allowed to drift slowly upward. Mean number of bar presses for cold and body-temperature water were compared under the various body-weight conditions, and in almost all cases the rats bar pressed at a higher rate for cold water. When these same animals were again deprived to 80% body weight, they showed an overwhelming preference for cold water over warm water in 10-min choice tests. A third experiment with these animals replicated Kapatos and Golds (1972) finding that rats offered either only warm water or only cold water in different test sessions drink more warm water than cold. The results of these experiments are consistent with the hypothesis that cold water is both more rewarding and more satiating than is body-temperature water, but it could be that the intake of cold water is terminated prematurely by the drop in body temperature which it produces.

Effects of intracisternal GABA or glutamic acid upon behavioral activity in the rat

It has been postulated that GABA acts as an inhibitor of command neurons, the activity of which initiates behavior. A prediction of this hypothesis is that elevations in functional GABA levels in the brain will cause decreases in behavioral output. Accordingly, in this study rats were injected intracisternally with either saline or one micromole of GABA or its excitatory precursor, glutamic acid, and behavioral activity in a novel environment was recorded as it habituated over the course of the subsequent 4 hours. The activity of the animals that were injected with GABA was greatly decreased, while the activity of the animals that were injected with glutamic acid was apparently unaffected, as compared to animals given saline. These data provide support for the hypothesis that GABA functions as an inhibitory neurotransmitter for behavior-activating command neurons.

Effects of intraventricular glutamic acid on the acquisition, performance, and extinction of an operant response, and on general activity

This study was designed to investigate the effects of intracerebral injections of glutamic acid on acquisition and extinction of a bar-press response, performance of that response, and behavioral activity. Nineteen food-deprived rats bearing chronic ventricular cannulae were tested in operant conditioning chambers or in an open field. Just prior to each testing session each animal was injected intraventricularly with 10 μl of either normal or acidified saline solution (control groups), or 10 μl of 100 mMol glutamic acid solution. Acquisition of the bar-pressing response by the glutamic acid group was significantly retarded as compared to the control groups, and the responding of the glutamic acid group was suppressed during the beginning of the first few sessions of testing on a fixedinterval schedule and during extinction. Other behavioral measures, such as operant level, performance of the response on a continuous schedule, performance on fixed-interval and extinction schedules except during the start of the first few sessions, and behavioral activity, were either unaffected or only slightly affected. It is concluded that interference with the normal neurophysiological activity of glutamic acid in the central nervous system interferes with learning and suppresses behavioral output in certain situations.

Airlicking: Thirsty rats prefer a warm dry airstream to a warm humid airstream☆

Abstract Water-deprived rats were trained to airlick in a chamber containing two drinking tubes through which air of ambient temperature and humidity was pumped. After each rat had learned to airlick and had developed a strong position preference for one of the tubes, the airstream emerging from that tube was heated to 42°C and saturated with humidity. The other airstream was heated to 42°C but its humidity was not increased. All rats developed a strong preference for licking the dry airstream and they maintained this preference throughout many position reversals. It is concluded that evaporative cooling of the orolingual tissues makes an important contribution to the reinforcement obtained from airlicking.

The role of hunger in schedule-induced polydipsia

Food-satiated rats bearing feeding-inducing hypothalamic electrodes were given one 45-mg food pellet per minute during 60-min daily sessions, with water continuously available. Electrical stimulation of the lateral hypothalamus (ESLH) was turned on for 3 or 15 sec, either concurrently with pellet delivery or 2-4 sec thereafter. Fifteen seconds of ESLH generated schedule-induced polydipsia (SIP), but 3 sec did not. When 15 sec of ESLH was delayed for 4 sec, strong SIP was manifested even though each ESLH was only initiated after each pellet had been consumed. It is concluded that postpellet hunger is necessary to produce SIP. Hunger during pellet consumption is neither a necessary nor a sufficient condition.

Principles of brain tissue engineering

It is often presumed that effects of neural tissue transplants are due to release of neurotransmitter. In many cases, however, effects attributed to transplants may be related to phenomena such as trophic effects mediated by glial cells or even tissue reactions to injury. Any conclusion regarding causation of graft effects must be based on the control groups or other comparisons used. In human clinical studies, for example, comparing the same subject before and after transplantation allows for many interpretations of the causes of clinical changes.