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J B Richards

Publications and source records attributed to J B Richards.

9 recordsLinked to original sources
PubMed1992

Fluoxetine attenuates the DL-fenfluramine-induced increase in extracellular serotonin as measured by in vivo dialysis.

Rats with hippocampal dialysis probes were treated with DL-fenfluramine (FEN), fluoxetine, or FEN with fluoxetine pre-treatment. FEN (12.5 mg/kg) increased extracellular serotonin (5-HT) from 0.4 +/- 0.04 to 25.2 +/- 4.16 pg/10 microliters. Fluoxetine (10.0 mg/kg) increased extracellular 5-HT levels from 0.4 +/- 0.05 to 2.4 +/- 0.33 pg/10 microliters. FEN-induced increases in extracellular 5-HT were attenuated by 66% with fluoxetine pre-treatment. This result supports the view that the 5-HT releasing properties of FEN are mediated by the 5-HT uptake transporter.

Animals↗
PubMed1992

The NMDA receptor antagonist MK-801 does not protect against serotonin depletions caused by high doses of DL-fenfluramine.

The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) has been shown to block methamphetamine (MA) induced damage to the dopamine (DA) and serotonin (5HT) systems of the brain. DL-Fenfluramine (FEN) is another potential neurotoxin but its long-term depletions are more selective to the 5HT system. To determine whether MK-801 protects against damage induced by FEN, we treated rats with FEN (4 injections of 12.5 mg/kg, at 1 h intervals) in conjunction with either saline or MK-801 (2 injections of 2.5 mg/kg, administered 15 min before and 90 min after the first FEN injection). Two weeks post-treatment, MK-801 alone caused a small but significant decrease in 5HT tissue concentrations in striatum and amygdala. FEN significantly reduced 5HT in all 8 brain regions studied. MK-801 + FEN did not protect against FEN-induced 5HT depletions in nucleus accumbens/olfactory tubercle, septum, frontal cortex, somatosensory cortex or hippocampus. MK-801 + FEN enhanced 5HT depletions in striatum, hypothalamus and amygdala. The differential protective effect of MK-801 between MA and FEN are discussed in terms of a possible dopaminergic mechanism.

Animals↗
PubMed1992

Fenfluramine-induced increases in extracellular hippocampal serotonin are progressively attenuated in vivo during a four-day fenfluramine regimen in rats.

Rats were administered 8 injections of 12.5 mg/kg fenfluramine over a 4-day period. Extracellular hippocampal serotonin levels were monitored in vivo during the 4-day treatment period. Predrug baseline serotonin levels were 0.6 +/- 0.17 pg/5 microliters; 60 min after the first fenfluramine injection extracellular serotonin levels were increased to 28.06 +/- 5.2 pg/5 microliters. Fenfluramine-induced increases in serotonin were substantially reduced on the 2nd through 4th days of the regimen. Baseline serotonin levels were increased on days 2 through 4 of the treatment regimen. In a separate group of animals post-mortem tissue concentrations of serotonin were measured 2 weeks after 1,2,4, or 8 injections of 12.5 mg/kg fenfluramine. There were decreases in serotonin tissue concentrations which were related to the number of fenfluramine injections administered. The in vivo dialysis and post-mortem tissue assay results are consistent with the view that fenfluramine is neurotoxic.

Animals↗
PubMed1991

A quantitative interresponse-time analysis of DRL performance differentiates similar effects of the antidepressant desipramine and the novel anxiolytic gepirone.

We describe an interresponse-time analysis of performance on a differential-reinforcement-of-low-rate 72-s schedule. This analysis compares the obtained interresponse-time distribution of individual rats to a corresponding random interresponse-time distribution. The random interresponse-time distribution is a negative exponential probability function; it predicts the relative distribution of interresponse times if the rat emitted the same number of responses randomly (i.e., with a constant probability) with respect to time. The analysis provides quantitative measures of peak location and dispersion of the interresponse times toward random performance. In Experiment 1, an unexpected outcome of this analysis was that the rats would have obtained more reinforcers had they responded at the same rate but randomly. Based on the interresponse-time analysis in Experiment 1, it was shown that rats trained on the differential-reinforcement-of-low-rate 72-s schedule could increase the number of reinforcers obtained in two ways: first, by a coherent shift of the interresponse-time distribution toward longer durations and, second, by dispersal of the interresponse times toward a random interresponse-time distribution. Experiment 2 applied the analysis described in Experiment 1 to the effects of desipramine and gepirone. Both drugs decreased response rate and increased reinforcement rate, but their effects on the distribution of interresponse times were different. The increase in reinforcement rate observed with desipramine was accompanied by a coherent shift of the reinforcement rate observed with gepirone was accompanied by dispersal of the interresponse-time distribution toward the random negative exponential prediction.

Animals↗
PubMed1990

Conditioned rotation: a behavioral analysis.

Rats trained to turn in circles have been used by a number of investigators to study brain dopamine metabolism. We report the results of a behavioral analysis of conditioned rotation and describe the apparatus used in our laboratory to train rats and monitor their performance. A novel discrimination procedure was used which required each rat to turn left in one training chamber with one set of stimulus conditions and right in a different chamber. Water-deprived animals were trained to circle for a water reward. Initial acquisition of this task required 11 days of training. At the end of acquisition, a discrimination test indicated that turning in the left and right directions was under stimulus control of the chamber environment. We found that trained turning had a highly stereotyped temporal organization with a rapid movement component during which the rat executed the turn, and a longer pause time component during which the rat consumed the water reinforcer.

Animals↗
PubMed1990

In vivo dialysis measurements of dopamine and DOPAC in rats trained to turn on a circular treadmill.

In vivo dialysis was used to measure extracellular fluid concentrations of dopamine and dihydroxyphenylacetic acid (DOPAC) in rats which were trained to run on a circular disk treadmill for water reinforcement. Turning resulted in bilateral increases in DOPAC in lateral striatum as well as nucleus accumbens/medial striatum. Dopamine release showed small but not significant increases at both sites. Changes in DOPAC release were not lateralized. Free drinking without circling also resulted in significant increases in DOPAC in these two brain areas. During free drinking, dopamine release was significantly increased in lateral striatum but not in nucleus/medial striatum. These experiments indicate that dopamine metabolism is increased in rat striatum and nucleus accumbens in animals running on circular treadmills as well as by free drinking.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Unilateral dopamine depletion causes bilateral deficits in conditioned rotation in rats.

Rats were trained to rotate for a water reward using a procedure which required each rat to turn in both the left and right directions. The rats were then lesioned with unilateral injections of 6-hydroxydopamine in the nigrostriatal bundle to produce unilateral dopamine depletion. Rats which had greater than 95% depletion had significant deficits in turning both ipsilateral and contralateral to the depleted side. Circling contralateral to the lesion was more impaired than circling ipsilateral to the lesion. All animals showed deficits in both the initiation of movement and in speed of turning. In addition, the rats displayed a chronic turning bias in the ipsilateral direction 16 weeks postlesion. These results indicate that unilateral dopamine depletion causes a variety of impairments in trained circling behavior. Although contralateral circling is most impaired, there is a significant decrease in ipsilateral performance. We conclude that normal conditioned circling behavior requires bilateral dopamine innervation.

Animals↗