Biomedical subjects

K L Drew

Publications and source records attributed to K L Drew.

26 records · Page 2Linked to original sources

PubMed1989

Differences in dopamine release and metabolism in rat striatal subregions following acute clozapine using in vivo microdialysis.

This study examined and compared the effects of acute clozapine administration over a range of doses on the release of dopamine (DA) and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in dorsolateral and fundus striata. Basal extracellular DA levels were significantly higher in the dorsolateral striatum. However, DOPAC levels were similar in both regions. Acute treatment with clozapine (40 mg/kg) was associated with an increase in extracellular dopamine in the dorsolateral striatum but not in the fundus. In contrast, an increase in extracellular DOPAC was seen in both regions following all doses of the drug; however, clozapine was more potent in the dorsolateral striatum than in the fundus. These results illustrate the functional heterogeneity of the striatum and in addition, indicate a possible dissociation between the effect of acute clozapine on DA release and DA metabolism.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1989

Characterization of gamma-aminobutyric acid and dopamine overflow following acute implantation of a microdialysis probe.

The present study characterized the voltage and calcium dependence of gamma-aminobutyric acid and dopamine overflow after the acute implantation of a microdialysis probe. Probes were implanted in dorsolateral striatum and globus pallidus. Experiments were performed under light halothane anesthesia. Basal, extracellular levels of GABA were not affected by tetrodotoxin (TTX) and were increased to 140 percent of basal values by calcium free Ringer. Basal, extracellular levels of dopamine were reduced to 14 percent of basal values by the addition of TTX and to 30 percent of basal values by the removal of calcium from the Ringer solution. The results suggest that in this in vivo preparation basal extracellular dopamine is largely of vesicular origin while GABA is not.

Animals↗

PubMed1988

Characterization of the associative nature of sensitization to amphetamine-induced circling behavior and of the environment dependent placebo-like response.

Amphetamine-induced circling behavior increases over the course of repeated administration of the drug; likewise, after repeated administration of amphetamine, an injection of saline prior to placement of the rat in the test apparatus previously associated with the pharmacologic effects of amphetamine will increase circling behavior. Experiments were designed to determine if either of these effects would respond to manipulation of the temporal contiguity between the test environment and the peak effects of amphetamine. The placebo-like response, in accordance with a Pavlovian conditioned response, was reduced by prior non-reinforced exposure to the test environment and subject to extinction. In contrast, the increase in the amphetamine-induced response was entirely dependent on the test environment but not affected by latent inhibition or extinction. These and previous findings indicate that the development and expression of the placebo-like response is the result of a Pavlovian associative process. Although amphetamine sensitization is environment dependent, it does not resemble a conditioned response in other respects.

Amphetamine↗

PubMed1988

Environment-dependent sensitization to amphetamine-induced circling behavior.

Sensitization to amphetamine-induced circling behavior in nonlesioned, female rats was studied. Experiments were designed to determine the effects of time spent in the test environment prior to and following the administration of amphetamine and of the time between injections of amphetamine on the environment-dependent nature of the sensitization process. One group of rats was allowed to habituate to the test apparatus prior to injection of the drug. In this group, the drug was administered in the apparatus and the rats remained there for the duration of drug action. Another group of rats was placed in the apparatus only during the time of peak drug action. These rats were administered amphetamine in their home cages and were not allowed time to habituate to the test apparatus. Amphetamine was administered 2 times and injections were separated by either 1 or 7 days. To determine if the sensitization was dependent on the environment in which the drug was previously experienced, one-half of each of these groups of rats were kept in their home cages following the first injection of amphetamine and experienced the effects of the second injection of amphetamine in the test apparatus. The other half experienced the effects of both injections of amphetamine in the test apparatus. Sensitization was found to occur only in rats that experienced the effects of the first drug injection in the test environment.

Analysis of Variance↗

PubMed1987

Classical conditioning of amphetamine-induced lateralized and nonlateralized activity in rats.

Amphetamine-induced lateralized activity (rotation) and nonlateralized activity (extra quarter turns) was classically conditioned in female rats using the test environment as the conditioned stimulus (CS) and 1.25 mg/kg d-amphetamine as the unconditioned stimulus. Conditioned lateralized activity extinguished more rapidly than nonlateralized activity. Also, d-amphetamine-induced nonlateralized activity was selectively decreased by a schedule of 50% partial reinforcement. These results indicate that the two d-amphetamine responses can be distinguished, that they are differentially affected by learning, and that a schedule of partial reinforcement can selectively attenuate one effect of a drug while leaving the other intact. In addition, haloperidol blocked conditioned lateralized activity; this suggests that the conditioned response may be, like the drug-induced response, mediated by dopamine.

Amphetamine↗

PubMed1986

Asymmetry in D-2 binding in female rat striata.

An asymmetry in D-2 receptor densities (Bmax) measured by [3H]N-methyl spiperone binding was found in striata from female Sprague-Dawley rats. The D-2 Bmax on the right side was on average 40% greater than the D-2 Bmax on the left side. This asymmetry is greater in magnitude and opposite in direction to that reported for males and is independent of directional preference exhibited during nocturnal circling.

Animals↗

PubMed1986

Differences in spontaneous and amphetamine-induced rotational behavior, and in sensitization to amphetamine, among Sprague-Dawley derived rats from different sources.

Nocturnal rotational behavior was found to vary severalfold among Sprague-Dawley derived rats obtained from seven different breeders; net rotations per night (18 hours) varied from 5.0 to 31.0 in males and from 6.2 to 42.4 in females. Rats from three sources were tested twice (a week between tests) for rotation induced by d-amphetamine. Rats from two sources showed evidence of sensitization to d-amphetamine, there being significantly greater rotation in response to the second dose than in response to the first dose; the d-amphetamine-induced rotational behavior of rats from the third source did not significantly change from one week to the next. However, the latter rats had a greater initial response to the first dose of d-amphetamine than did rats from the other two breeders. Further analysis revealed that, among rats from all three breeders, rats rotating weakly in response to d-amphetamine on the first test tended to rotate more on the second test whereas rats rotating strongly in response to d-amphetamine on the first test tended to rotate less on the second test. This relationship was found to apply to previously collected data as well and was discussed with reference to a proposed mechanism involving asymmetry in sensitization to d-amphetamine-induced release of striatal dopamine. Interindividual differences among seemingly similar experimental subjects appear to contribute importantly to reported differences in results among laboratories.

Animals↗

PubMed1983

Learning impairments following postnatal exposure to benzene.

Two groups of male hooded rats of the Sprague-Dawley strain were administered 550 mg/kg of benzene in corn oil or pure corn oil on Days 9, 11, and 13 postpartum. When tested on problems of the Hebb-Williams closed-field maze-learning task, the rats previously exposed to benzene manifest significantly impaired learning ability when compared to control rats in the total number of error zones entered over the 12 test problems. No significant differences were found in food consumption, water consumption, or weight gain. Moreover, none of the overt manifestations characteristic of acute or chronic benzene exposure were observed. Learning deficits were exhibited at levels of exposure previously considered subtoxic.

Animals↗