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Biomedical subjects

R J Barrett

Publications and source records attributed to R J Barrett.

At least 127 records · Page 7Linked to original sources
PubMed1980

Effects of chronic amphetamine or reserpine on self-stimulation responding: animal model of depression?

The mood-altering properties of amphetamine (AMPH) in humans (euphoria and depression) have been postulated to be related to the increases and decreases respectively which this drug produces in the sensitivity of the reward system of the brain. The present study further evaluated this relationship by testing the effects of chronic reserpine (RES), another treatment that produces depression in humans, on self-stimulation responding. Separate groups of animals implanted with stimulating electrodes in the medial forebrain bundle were administered daily injections of saline, d-AMPH (5 mg/kg X 7 days followed by 10 mg/kg X 7 days), or RES (0.05 mg/kg X 18 days). At treatment termination, both drug groups showed a significant elevation of the reinforcement threshold, with no recovery occurring during 18 subsequent days. Thus, drug-induced depression of self-stimulation responding may serve as an animal model for studying the underlying physiological basis for clinical depression, or at the very least, for drug-induced depression.

Animals↗
PubMed1980

Reward system depression following chronic amphetamine: antagonism by haloperidol.

The effect of pre-treatment with haloperidol, a dopamine antagonist, on chronic amphetamine's suppression of intra-cranial self-stimulation of the lateral hypothalamus was investigated. Rats treated with 15 mg/kg d-amphetamine per day for seven days displayed a marked increase in reward threshold for electrical brain stimulation responding with an accompanying suppression of response rate. This disruption of intracranial self-stimulation responding was not observed when 30 min prior to each amphetamine injection, animals were injected with 1.0 mg/kg of haloperidol. This study demonstrates that post-synaptic mechanisms play an integral role in the development of chronic amphetamine depression, and suggests that changes at the dopamine receptor are involved in this reward system alteration.

Amphetamine↗
PubMed1980

Development of tolerance to the rewarding effects of self-administered S(+)-amphetamine.

Rats were implanted with chronic intravenous cannulae and trained to bar press for intravenous, self-administered S(+)-amphetamine (AMPH). After establishment of a steady baseline at 0.25 mg/kg/reinforcement, the animals were removed from the test situation and subsequently injected three times a day four days with increasing amounts of AMPH (total=78 mg/kg). Thirty-six hours after the last injection, the animals were tested for tolerance to self-administered AMPH, and all the animals increased the amount of drug intake by at least 45% over baseline. The brain disppearance of a 10 mg/kg IV dose of AMPH was measured for the chronic AMPH and saline treated subjects to test for the possibility of enzyme induction. No differences were found. These data indicate that drug self-administration in rats is a useful paradigm to study tolerance to the rewarding effects of AMPH and indicate that drug self-administration in rats is a useful paradigm to study tolerance to the rewarding effects of AMPH and may be useful in understanding the mechanisms mediating the mood elevating properties of the drug observed in humans.

Amphetamine↗
PubMed1978

Tolerance to amphetamine's facilitation of self-stimulation responding: anatomical specificity.

Further work on the phenomenon reported by Leith and Barrett, wherein tolerance was shown to develop to the well-known D-amphetamine-induced facilitation of self-stimulation, clearly indicates that the development of such tolerance is dependent on the location of the stimulating electrode. Thirty-seven Fisher or Harlan rats were trained to bar press for hypothalamic stimulation (60 Hz, AC). Following several sessions during which small doses of D-amphetamine were administered to demonstrate facilitation, the subjects were placed on a 4-day D-amphetamine regimen. During this time they were given three daily injections of continuously increasing doses of D-amphetamine (total 78 mg/kg). Subsequent tolerance was shown for electrodes stimulating dorsal or medial hypothalamic structures (H2 field of Forel, dorsal medial forebrain bundle, medial hypothalamic nuclei), but did not develop with ventral or lateral hypothalamic stimulation sites (fornix, ventral medial forebrain bundle).

Animals↗
PubMed1977

Effects of thiamin deficiency on acetylcholine levels and utilization in vivo in rat brain.

Cerebral regional acetylcholine (ACh) levels and utilization were studied in vivo in thiamin deficient (TD), pair-fed asymptomatic (PFC) and ad libitum fed control (ALC) rats. ACh levels in the cortex, corpus striatum, midbrain, diencephalon and brainstem of TD rats were comparable to those observed in the control groups. However, ACh utilization was slightly to moderately (10-41%) decreased in cortex, midbrain, diencephalon and brainstem. The decrease was significantly different in the midbrain of TD rats as compared to PFC and ALC rats.

Acetylcholine↗
PubMed1976

Amphetamine and the reward system: evidence for tolerance and post-drug depression.

Existing reports of tolerance to the behavioral effects of d-amphetamine are most parsimoniously interpreted as reflecting behavioral adaptation to the disruptive effects of the drug rather than physiological tolerance. The present study shows that physiological tolerance does develop to the facilitation of self-stimulation behavior which the drug produces. Rats were trained to bar-press for electrical stimulation of the medial forebrain bundle and tested for facilitation of responding following the administration of 0.25 or 0.50 mg/kg d-amphetamine. Testing was terminated for 4 days during which increasing doses (1.0-12.0 mg/kg) of the drug were given. 16 h after the last injection, the test doses (0.25 or 0.50 mg/kg) no longer produced facilitation of self-stimulation. In addition, testing on the following day with no further drug administration showed a depression of responding indicating depression of the sensitivity of the reward system of the brain.

Animals↗
PubMed1975

Effects of hippocampal microinjections of D-amphetamine and scopolamine on active avoidance behavior in rats.

Rats received bilateral injections of 20 or 40 mug. of d-amphetamine or scopolamine into the dorsal or ventral hippocampus prior to each of 8 daily training sessions in a discriminated Y-maze active avoidance task. Scopolamine, but not d-amphetamine, facilitated avoidance responding in both sites, with the effect being greatest following administration of 20 mug. into the dorsal hippocampus. On Days 9 and 10, all animals received saline injections and were tested for transfer of responding to the nondrug state. A decrement of performance occurred irrespective of whether the drug had facilitated avoidance responding. The performance changes were greater following termination of scopolamine than d-amphetamine injections, and in no case were so great as those previously reported following peripheral injections of the drugs.

Animals↗