PubMed Health⌕ Search

Biomedical subjects

J N Carlson

Publications and source records attributed to J N Carlson.

36 records · Page 2Linked to original sources
PubMed1992

Effects of ibogaine on acute signs of morphine withdrawal in rats: independence from tremor.

Because of the claim that ibogaine suppresses the symptoms of "narcotic withdrawal" in humans, the effect of ibogaine on naltrexone-precipitated withdrawal signs in morphine-dependent rats was assessed. Morphine was administered subcutaneously through implanted silicone reservoirs for 5 days. Ibogaine (20, 40 or 80 mg/kg, i.p.) or saline was administered 30 min prior to challenge with naltrexone (1 mg/kg, i.p.) and withdrawal signs were counted for the following 2 hr. Ibogaine (40 and 80 mg/kg) significantly reduced the occurrence of four signs (wet-dog shakes, grooming, teeth chattering and diarrhea) during naltrexone-precipitated withdrawal; three other signs (weight loss, burying and flinching) were unaffected. Ibogaine induces head and body tremors lasting for 2-3 hr and the tremors might have interfered with the expression of opioid withdrawal. To examine this issue, another experiment was conducted in which ibogaine (40 mg/kg) or saline was administered 4 hr prior to challenge with naltrexone. Although there was a complete absence of tremors, ibogaine still significantly reduced the occurrence of the same four signs of withdrawal.

Acute Disease↗
PubMed1991

Side and region dependent changes in dopamine activation with various durations of restraint stress.

Exposure to various mild stressors has been shown to result in the activation of dopamine containing neuronal systems projecting to the medial prefrontal cortex (PFC), to a lesser extent the nucleus accumbens septi/olfactory tubercle (NAS) and, in a few studies, the striatum. It has also been shown that dopamine (DA) systems on different sides of the PFC are successively activated as stressors are prolonged. We have therefore examined the effects of variation in the duration of a restraint stressor (15, 30 and 60 min) on region and side dependent alterations in DA utilization in the PFC, NAS and striatum. Increases in the concentrations of the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and/or homovanillic acid (HVA) or in their ratios with DA were seen in all regions examined with the largest effects occurring in the PFC and lesser effects in the NAS and striatum. In each region, the magnitude of these effects varied with time of restraint exposure. In the PFC, lateralized alterations in HVA and DA were seen over time with effects progressing from a left greater than right involvement at 15 min to a right greater than left involvement at 60 min. These results are discussed with reference to side and region dependent effects on brain DA systems as stressors are prolonged and the implications they may have for lateralized regional brain activity associated with stressor precipitated psychiatric disease.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Brain laterality as a determinant of susceptibility to depression in an animal model.

Rats exposed to stressors that cannot be controlled may develop a deficit in their ability to subsequently learn to control a new stressor. This phenomenon is known as 'learned helplessness' and is a well-accepted animal model of depression. Evidence is presented showing that rats having different directional biases of brain laterality, as indicated in tests of rotational behavior, differ greatly in their response to stressors and to the lack of stressor control. Differences in brain laterality appear to be an important source of variability within the animal model of depression. As with humans, only some rats are vulnerable to depression-like symptoms. These findings are relevant to biological theories of depression that are based upon lateralized specialization of the human brain for affect.

Amphetamine↗
PubMed1991

Effects and aftereffects of ibogaine on morphine self-administration in rats.

Ibogaine, a naturally occurring alkaloid, has been claimed to be effective in treating addition to opiate and stimulant drugs. As a preclinical test of this claim, the present study sought to determine if ibogaine would reduce the intravenous self-administration of morphine in rats. Ibogaine dose dependently (2.5-80 mg/kg) decreased morphine intake in the hour after ibogaine treatment (acute effect) and, to a lesser extent, a day later (aftereffect); while the acute effect could be attributed to abnormal motor behavior (whole body tremors), the aftereffect occurred at a time when ibogaine should have been entirely eliminated from the body and when there was no obvious indication of ibogaine exposure. In some rats, there was a persistent decrease in morphine intake for several days or weeks after a single injection of ibogaine; other rats began to show such persistent changes only after two or three weekly injections whereas a few rats were apparently resistant to prolonged aftereffects. Aftereffects could not be attributed to a conditioned aversion. Although ibogaine also depressed responding acutely in rats trained to bar-press for water, there was no evidence of any aftereffect a day or more later; the interaction between ibogaine and morphine reinforcement was therefore somewhat specific. Further studies are needed to characterize the nature of the ibogaine-morphine interaction as well as to determine if ibogaine also affects the self-administration of other drugs.

Animals↗
PubMed1991

Acute administration of diazepam and buspirone in rats trained on conflict schedules having different degrees of predictability.

The anti-conflict activities of diazepam and buspirone were examined on three schedules designed to condition the suppression of licking. The schedules differed in the degree to which they predicted (signalled) the presentation of a conflict inducing electric shock. The first study investigated the effects of three doses of diazepam (0.5, 2, and 5 mg/kg IP) on a predictable, a moderately predictable, and an unpredictable schedule of shock presentation. Diazepam induced a significant increase from baseline in licking during the shock component on all three schedules. These anticonflict effects were the most consistent on the predictable schedule, and least consistent on the unpredictable schedule. A second experiment investigated the anticonflict activity of three doses of buspirone (0.125, 0.25, and 0.625 mg/kg SC) on each of these three schedules. The predictable and moderately predictable schedules failed to detect anticonflict activity at any dose of buspirone. However, the lowest dose (0.125 mg/kg) of buspirone increased shocked licking and the highest dose (0.625 mg/kg) decreased shock component licking on the unpredictable schedule. Thus the unpredictable schedule was sensitive to both anticonflict (anxiolytic) and proconflict (anxiogenic) effects of buspirone.

Animals↗
PubMed1991

The effects of acute administration of gepirone in rats trained on conflict schedules having different degrees of predictability.

The anticonflict activity of gepirone, a putative anxiolytic and antidepressant, was examined on three schedules which conditioned the suppression of licking. The novel schedules differed in the degree to which they predicted (signalled) the presentation of a conflict-inducing electric shock. Three doses of gepirone (1.25, 2.5, and 5 mg/kg SC) were evaluated on a predictable, a moderately predictable, and an unpredictable schedule of shock presentation. Gepirone induced a nondose-dependent increase from baseline in punished licking on the predictable schedule on the last two days of a five-day test period. The lowest dose (1.25 mg/kg) of gepirone induced a significant increase in punished licking on the moderately predictable schedule on the last two days of testing. The highest dose (5 mg/kg) induced initial decreases in overall responding on this schedule. However, responding returned to baseline over the course of the four days of testing. When administered to rats trained on an unpredictable schedule of shock presentation, all doses of gepirone induced an initial decrease from baseline. The lowest dose group returned to baseline control response levels over the next four days, whereas the suppressive effects of the higher doses persisted. The initial decrease in responding observed on all schedules may be due to the effects of gepirone on motor functioning. However, the 2.5-mg/kg dose induced a proconflict or anxiogenic effect on the last test day (decreased punished responding alone) on the unpredictable schedule, while inducing an anticonflict effect on the predictable one. The unpredictable schedule is sensitive to detecting decreases as well as increases in punished responding and as such may be a unique conflict model for evaluating novel anxiolytics.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Right-sided population bias in male rats: role of stress.

Recent studies have shown that rats develop a pronounced right-sided population bias when tested repeatedly over several days in a shock-escape T-maze paradigm. In the present study we sought to determine if this bias was the result of learning or of the repeated exposure to a stressor (footshock). Rats were tested in the T-maze for 5 trials on each of 6 consecutive days. One group of rats (HS-C) was allowed a free left or right choice on each trial whereas another group of rats (HS-A) was forced to alternate left and right turns on each trial for the first 5 days of testing and then allowed a free choice on Day 6. The population and individual laterality of the HS-A group did not differ from that of the HS-C group, indicating that learning does not account for the biases. A third group of rats (LS-C) was tested using a lower shock level; this decrease in stressor intensity delayed the development of a right-sided population bias without affecting the development of individual laterality. These results indicate that repeated exposure to a stressor, rather than learning, is primarily responsible for the marked right-sided population bias observed in the T-maze.

Animals↗
PubMed1989

Regional changes in brain dopamine and serotonin metabolism induced by conditioned circling in rats: effects of water deprivation, learning and individual differences in asymmetry.

Rats were trained, using water reinforcement, to turn in circles (rotation) during 1 h daily test sessions. After achieving criterion performance (100 full turns per hour) for at least 10 consecutive sessions, rats were sacrificed 20 min after starting a session and levels of dopamine, DOPAC (3,4-dihydroxyphenylacetic acid), serotonin, and 5-HIAA (5-hydroxyindoleacetic acid) were assayed in nigrostriatal (corpus striatum), mesolimbic (nucleus accumbens) and mesocortical (medial prefrontal cortex) brain regions. Other control groups of rats were comparably water deprived or satiated at the time of sacrifice. Although, as previously reported, evidence of 'two populations' of rats was again apparent with respect to the relationship between direction of spontaneous turning and asymmetry in striatal dopamine levels, there were no lateralized effects of operant rotational training on striatal dopamine and DOPAC levels nor on the DOPAC/dopamine ratio. There were, however, bilateral neurochemical effects of both rotational training and water deprivation in striatum: an increase in the 5-HIAA/serotonin ratio in both sexes was attributable to learning whereas an increase in the DOPAC/dopamine ratio in males was attributed to water deprivation. A bilateral decrease in the DOPAC/dopamine ratio in the mesolimbic and mesocortical regions of both sexes was also induced by water deprivation. The only lateralized neurochemical changes associated with learning to rotate in the operant task occurred in the medial prefrontal cortex: in both sexes, dopamine levels were higher in the ipsilateral than in the contralateral cortex and the DOPAC/dopamine ratio was greater in the contralateral than in the ipsilateral cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Cerebral lateralization as a source of interindividual differences in behavior.

Cerebral laterality can no longer be considered an exclusively human trait, as over the last 15 years there has been an emergence of data to suggest that animal brains are also lateralized. Morphologic, chemical and behavioral indices of brain asymmetry in the rodent have been reported, and it is suggested that variations in the magnitude and direction of these indices are determined by a complex interaction of genetic, hormonal and experiential factors. Interindividual differences in cerebral laterality have been shown to covary with, or predict, individual differences in spatial behavior and stress reactivity, as well as susceptibility to stress pathology and drug sensitivity. Such findings suggest that it is possible to study individual differences in lateralized brain function through the use of animal models.

Animals↗
PubMed1989

Dose-dependent and baseline-dependent conditioning with d-amphetamine in the place conditioning paradigm.

The place conditioning paradigm was used to evaluate the positively reinforcing effects of d-amphetamine. During conditioning, female rats were injected (IP) with saline or one of five doses (0.625-5 mg/kg) of d-amphetamine (d-A) and confined to the initially non-preferred side of the testing apparatus. The highest dose of d-A failed to produce a significant preference. The four middle doses of the drug induced a similar preference. A significant increase from baseline was observed on the 4th post-conditioning test day in the five drug groups and controls when given an injection of 1.5 mg/kg d-A 15 min prior to placement in the chamber. Control and drug groups were separated into high and low initial preference sub-groups. Place preferences were more readily induced by d-A in the subgroups with initially high baseline preferences. These findings as well as those of others led us to conclude that the place conditioning paradigm is a somewhat problematic way of measuring drug reinforcement and that the effects observed may not solely be the result of the conditioning of the drug's reinforcing properties to a particular environment.

Animals↗
PubMed1988

Basal and amphetamine-induced asymmetries in striatal dopamine release and metabolism: bilateral in vivo microdialysis in normal rats.

In vivo microdialysis was used to monitor bilaterally the release of dopamine and its metabolites 3,4-dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) in the striata of both anesthetized and awake, freely moving female rats. Under baseline conditions, an asymmetry in dopamine release was reciprocally related to an asymmetry in DOPAC. Baseline dopamine and DOPAC asymmetries were predictive of the preferred direction of amphetamine-induced rotation: the striatum having higher dopamine and lower DOPAC was contralateral to the preferred direction of rotation. Amphetamine (D-amphetamine sulfate, 1.25 mg/kg) enhanced dopamine release and decreased DOPAC and HVA; the increase in dopamine was greater in the ipsilateral striatum. Effects in anesthetized and awake rats were similar. Variations in rotation and in the dopamine asymmetry after amphetamine were correlated across time within individual awake rats.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Food deprivation alters dopamine utilization in the rat prefrontal cortex and asymmetrically alters amphetamine-induced rotational behavior.

The effects of 24 and 48 h of food deprivation on changes in the activity of dopaminergic (DAergic) neurons and D-amphetamine-induced rotational behavior were studied in male and female Long-Evans rats. Food deprivation selectively altered 3,4-dihydroxyphenylacetic acid (DOPAC) in the medial prefrontal cortex (PFC) but not in the nucleus accumbens or striatum: PFC DOPAC was significantly increased and decreased bilaterally after 24 and 48 h of food deprivation, respectively. Left greater than right hemispheric asymmetries were seen for DOPAC and DOPAC/DA in the control animals. In a separate experiment, 24 h of food deprivation enhanced right rotational behavior, while 48 h significantly increased left rotational behavior. The results are discussed in terms of food deprivation's effects on mesocortical DAergic neurons, previous work on cortical modulation of striatal function and how these effects on rotational behavior may be determined by brain asymmetry.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Selective enhancement of dopamine utilization in the rat prefrontal cortex by food deprivation.

Previous studies have indicated that food deprivation exerts various effects on brain neurotransmitters and that mild stress causes a selective enhancement of dopamine activity in the rat medial prefrontal cortex. In the present study it was found that in rats 24 h of food deprivation produced an increase in levels of the dopamine metabolite 3,4-dihydroxyphenylacetic acid in the medial prefrontal cortex but not in the nucleus accumbens or caudate-putamen. This selective increase in mesocortical dopamine activity is comparable to that found with mild footshock stress exposure and indicates that food deprivation may function as a stressor.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Food deprivation and stimulant self-administration in rats: differences between cocaine and d-amphetamine.

The effects of food deprivation (24 h) on response rates of rats self-administering d-amphetamine and cocaine were compared. Food deprivation clearly increased rates of responding for both drugs but did so to a significantly greater extent for cocaine than for d-amphetamine. Consistent with other findings, the results suggest that the neural substrates underlying cocaine and d-amphetamine reinforcement are not identical.

Animals↗
PubMed1987

Exposure to low doses of the environmental chemical dieldrin causes behavioral deficits in animals prevented from coping with stress.

Experiments were conducted which assessed the effects of low doses of an environmental contaminant in conjunction with various forms of stress. Rats were given acute doses (0, 0.5, 1.5, 4.5 mg/kg) of the chemical dieldrin and subsequently exposed to a series of 40 escapable shocks, identical inescapable shocks, or no shock in an operant chamber. Eight hours later, the subjects were re-exposed in a shuttlebox to footshock which was escapable upon performance of an FR-2 shuttle response. Escape deficits which were related in magnitude to the size of the dieldrin dose were found in the inescapable shock group but not in the escapable shock or no shock groups. The data suggest that experience with the lack of control over stress is critical in determining the behavioral effects of the agent and that the behavioral effects caused by uncontrollable stress may be exacerbated by concurrent exposure to such compounds. These results are discussed in terms of previous studies on the behavioral actions of dieldrin, the response to uncontrollable stress and the common neuronal systems that may be involved.

Animals↗
PubMed1987

Changes in d-amphetamine elicited rotational behavior in rats exposed to uncontrollable footshock stress.

Male and female rats, selected on the basis of their rotational behavior in response to d-amphetamine, were exposed to either escapable footshock stress, inescapable footshock stress or no stress and were then given a shuttlebox escape task on the subsequent day. Following testing, the magnitude and direction of the animals' rotational responses to d-amphetamine were determined again. Inescapable footshock stress induced a selective change in the direction and intensity of rotational behavior that was dependent upon the subjects' sex and preexisting rotational bias. Right-rotating males and left-rotating females shifted their directional bias toward the opposite side, while left-rotating males and right-rotating females displayed increased rotation in their pre-stress direction. Significant correlations were also noted between the intensity of pre-stress rotational behavior and performance on the shuttlebox shock escape task. The results are discussed with respect to stress' actions on the mesocortical dopamine system and how this system's sex-dependent asymmetrical organization may subserve part of the organism's general reaction to uncontrollable stress.

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↗