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Biomedical subjects

T E Robinson

Publications and source records attributed to T E Robinson.

At least 91 records · Page 5Linked to original sources
PubMed1988

The long-term effects of repeated amphetamine treatment in vivo on amphetamine, KCl and electrical stimulation evoked striatal dopamine release in vitro.

Exposure to amphetamine (AMPH) in vivo produces an enduring enhancement ('sensitization') in AMPH-stimulated striatal DA release in vitro. Experiments were conducted to determine whether striatal DA release evoked by neuronal depolarization is altered by AMPH pretreatment in a similar manner. It was found that AMPH pretreatment produced a long-lasting (at least one week) enhancement in striatal DA release evoked by AMPH, KCl or electrical field stimulation. In contrast, the basal rate of DA efflux was not altered by pretreatment condition. A mechanism by which a single change in the intracellular distribution of DA could enhance both AMPH- and depolarization-induced DA release is proposed.

Amphetamine↗
PubMed1988

Intraventricular microdialysis: a new method for determining monoamine metabolite concentrations in the cerebrospinal fluid of freely moving rats.

A new method is described to estimate the cerebrospinal fluid (CSF) concentrations of monoamine metabolites (dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA] in the lateral ventricle of freely moving rats by use of in vivo microdialysis. Both the baseline concentrations of these metabolites and the rate of dopamine (DA) turnover (estimated by the accumulation of total DA metabolites after 200 mg/kg probenecid) were within the range reported when other methods were used to sample CSF. A series of preliminary studies were conducted to demonstrate that this method can be used to repeatedly sample CSF, and to show that the method is sensitive to local changes in dopaminergic activity induced by lesions, drugs or grafts. (1) Unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra produced a significant decrease in the CSF concentrations of DOPAC and HVA ipsilateral to the lesion, relative to the contralateral side or to concentrations in animals without lesions. (2) When left and right lateral ventricles were sampled simultaneously in animals with a unilateral 6-OHDA lesion, haloperidol induced an increase in DOPAC and HVA concentrations in CSF on both sides of the brain. Interestingly, the haloperidol-induced increase in CSF concentrations of DA metabolites was greater adjacent to the intact striatum of rats with unilateral 6-OHDA lesions than in animals with no lesion. (3) Finally, in animals with adrenal medulla tissue grafted into the lateral ventricle there was an increase in the CSF concentration of DOPAC compared to pregraft values or to those of animals with control grafts.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Intra-arterial and cuff blood pressure responses during incremental cycle ergometry.

Brachial intra-arterial blood pressure [systolic (AS) and diastolic (AD)] and cuff blood pressure [systolic (CS) and fourth- and fifth-phase diastolic (CD)] were simultaneously measured by a single observer in 13 middle-aged men during 1-min incremental cycle exercise. On the average, the mean AS exceeded the mean CS by 10 to 11 mm Hg, while the mean AD exceeded the average fourth and fifth CD by 5 and 13 mm Hg, respectively. During incremental exercise, AS, CS, AD, and fourth-phase CD increased, while fifth-phase CD decreased. We also measured intra-arterial blood pressure in nine young adult men smokers during 1-min incremental cycle exercise. In both groups, the average intra-arterial blood pressures increased in a relatively linear fashion from rest to maximal exercise: AS change = 74 +/- 5 mm Hg (SE) and AD change = 28 +/- 3 mm Hg for young men; AS change = 59 +/- 5 mm Hg and AD change = 12 +/- 3 mm Hg for middle-aged men. In this population of middle-aged smokers, intra-arterial mean blood pressure during exercise approximated diastolic plus 2/5 pulse pressure for intra-arterial measures or diastolic plus 1/2 pulse pressure for cuff measures rather than the traditional formula of diastolic plus 1/3 pulse pressure.

Adult↗
PubMed1987

The effects of footshock stress on regional brain dopamine metabolism and pituitary beta-endorphin release in rats previously sensitized to amphetamine.

The repeated intermittent administration of amphetamine (AMP) produces an enduring enhancement in the response of dopamine (DA) systems in the brain to a subsequent "challenge" with amphetamine. However, former amphetamine addicts are not only hypersensitive to amphetamine, but also to "physical or psychological stress". This suggests that sensitization to amphetamine may change the response of DA neurons in brain to subsequent stress. To explore this idea, the effects of footshock stress on regional metabolism of DA in brain, and on the concentrations of plasma beta-endorphin and N-acetylated beta-endorphin, were studied in rats previously exposed to amphetamine or saline. It was found that: Prior treatment with amphetamine produced enduring (at least 7 days) changes in the dopaminergic response to footshock in the medial frontal cortex, hypothalamus, dorsolateral striatum and nucleus accumbens. Generally, rats pretreated with amphetamine showed a greater initial reduction in concentrations of DA in response to footshock, and a greater elevation in concentrations of metabolites of DA and/or metabolite/transmitter ratios, compared to nonhandled control rats. In some regions of the brain repeated injections of saline produced changes in the response to subsequent footshock that were comparable to those produced by amphetamine. Prior treatment with amphetamine enhanced the release of beta-endorphin and N-acetylated beta-endorphin from the pituitary elicited by footshock stress. It is concluded that repeated intermittent treatment with amphetamine or stress (injections of saline) produce enduring changes in the response of DA neurons and the pituitary to subsequent stress. These changes may be responsible for the hypersensitivity to stress reported in former amphetamine addicts, and in rats previously sensitized to amphetamine.

Amphetamine↗
PubMed1987

Long-lasting effects of escalating doses of d-amphetamine on brain monoamines, amphetamine-induced stereotyped behavior and spontaneous nocturnal locomotion.

The repeated intermittent administration of relatively low doses of amphetamine (AMPH) produces an enduring hypersensitivity to the motor stimulant effects of AMPH (behavioral sensitization), and this is accompanied by enhanced mesotelencephalic dopamine (DA) utilization/release. In contrast, chronic treatment with very high doses of AMPH does not produce sensitization, but is neurotoxic, resulting in the depletion of brain DA (and often other monoamines). However, gradually escalating doses of AMPH provide protection against the neurotoxic effects of higher doses given later. Therefore, the purpose of the present experiment was to determine if a regimen of gradually escalating doses of AMPH, culminating in much higher doses than usually used to study sensitization, would produce neural and behavioral changes associated with AMPH neurotoxicity (DA depletion) or behavioral sensitization (increased DA utilization). Female rats were given 60 injections (2/day) of increasing (1 to 10 mg/kg) doses of d-AMPH, culminating in rats receiving 20 mg/kg/day for four consecutive days. This treatment did not deplete brain DA or serotonin, but did produce a long-lasting enhancement (at least 12 days) in striatal and nucleus accumbens DOPAC concentrations, and DOPAC/DA ratios. These neurochemical changes were accompanied by an enduring hypersensitivity to the stereotypy-producing effects of a subsequent AMPH 'challenge.' In contrast to this enhanced response to a challenge, AMPH-pretreated rats showed a marked reduction in spontaneous nocturnal motor activity. It is concluded that rats can be given escalating doses of AMPH, which mimic to some extent the AMPH 'runs' common in addicts and that this produces neural and behavioral changes consistent with the development of sensitization; not neurotoxicity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Enduring changes in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis.

Some people who repeatedly use stimulant drugs, such as amphetamine (AMPH), develop an AMPH-induced psychosis that is similar to paranoid schizophrenia. There has been, therefore, considerable interest in characterizing the effects of chronic stimulant drug treatment on brain and behavior in non-human animals, and in developing an animal model of AMPH psychosis. A review of this literature shows that in non-human animals chronic AMPH treatment can produce at least two different syndromes, and both of these have been proposed as animal models of AMPH psychosis. The first syndrome is called 'AMPH neurotoxicity', and is produced by maintaining elevated brain concentrations of AMPH for prolonged periods of time. AMPH neurotoxicity is characterized by what has been termed 'hallucinatory-like' behavior, which occurs in association with brain damage resulting in the depletion of striatal DA and other brain monoamines. The second syndrome is called 'behavioral sensitization', and is produced by the repeated intermittent administration of lower doses of AMPH. Behavioral sensitization is characterized by a progressive and enduring enhancement in many AMPH-induced behaviors, and is not accompanied by brain damage or monoamine depletion. It is argued that the changes in the brain and behavior associated with the phenomenon of behavioral sensitization provide a better 'model' of AMPH psychosis than those associated with AMPH neurotoxicity. Much of the review involves a critical analysis of hypotheses regarding the biological basis of behavioral sensitization. Research on this question has focused on mesotelencephalic DA systems, and suggestions that behavioral sensitization is accompanied by: an increase in postsynaptic DA receptors; an increase in DA synthesis; an increase in DA utilization and/or release; and a decrease in DA autoreceptors, are evaluated. It is concluded that there is not convincing evidence for an increase in postsynaptic DA receptors or in DA synthesis in animals sensitized to AMPH. In contrast, there is strong evidence to support the notion that behavioral sensitization is due to enhanced mesotelencephalic DA release, especially upon re-exposure to the drug. The evidence that this enhancement in DA release is due to autoreceptor subsensitivity was found to be equivocal, and therefore other hypotheses should be entertained. Lastly, evidence is discussed in support of the idea that behavioral sensitization is not unique to the psychopharmacology of stimulant drugs, but may be produced by many environmental stimuli that directly or indirectly activate brain catecholamine systems.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗
PubMed1986

Sex differences in the effects of gonadectomy on amphetamine-induced rotational behavior in rats.

The effects of gonadectomy on amphetamine-induced rotational behavior were studied in male and female rats. Different systemic doses were used to produce equivalent brain concentrations of the drug in each group, thereby controlling for sex differences in the metabolism of amphetamine. Ovariectomy of female rats significantly attenuated amphetamine-induced rotation, whereas castration of males was without effect. The results support the idea that in females, the endogenous gonadal hormones facilitate functional activity in the mesostriatal dopamine system.

Amphetamines↗
PubMed1986

The propensity for nonregulatory ingestive behavior is related to differences in dopamine systems: behavioral and biochemical evidence.

Previous research has shown that animals predisposed to eat and drink in response to electrical stimulation of the lateral hypothalamus (ESLH) are similarly predisposed to drink excessively when tested for schedule-induced polydipsia. The eating and drinking elicited by both experimental paradigms appears to be unrelated to homeostatic need and has been called nonregulatory ingestive behavior. In this study, the relation between properties of dopaminergic neural systems and the predisposition to exhibit nonregulatory ingestive behavior was investigated. It was found that rats that eat and drink during ESLH show greater behavioral sensitization to a series of amphetamine injections that those that do not exhibit ingestive behavior during ESLH. In addition, footshock stress produced a greater increase in forebrain dopamine utilization in rats that engaged in nonregulatory ingestive behavior. This evidence is consistent with the hypothesis that there are individual differences in the responsiveness of forebrain dopamine systems that are related to the behavioral predisposition to exhibit nonregulatory ingestive behavior.

Animals↗
PubMed1985

Enduring enhancement in frontal cortex dopamine utilization in an animal model of amphetamine psychosis.

It is reported that in rats the repeated intermittent administration of amphetamine produces a long-lasting enhancement in medial frontal cortex dopamine utilization. This change in mesocortical dopamine activity may be involved in the behavioral sensitization produced by psychomotor stimulant drugs, and some of the cognitive abnormalities (e.g. amphetamine psychosis) associated with stimulant drug abuse in humans.

Amphetamine↗
PubMed1985

Sensitization to stress: the enduring effects of prior stress on amphetamine-induced rotational behavior.

In rats with a unilateral 6-OHDA lesion of the substantia nigra exposure to footshock or immobilization stress produced a long-lasting enhancement in the rotational behavior evoked by a subsequent injection of amphetamine. However, the effect was dependent on the environmental context in which stress was applied. It is suggested that stress may induce enduring changes in brain and behavior similar to those produced by psychomotor stimulant drugs.

Amphetamine↗
PubMed1985

Involvement of nigrostriatal dopamine neurons in the contraversive rotational behavior evoked by electrical stimulation of the lateral hypothalamus.

This experiment was conducted to determine if nigrostriatal dopamine (DA) neurons are necessary for the contraversive rotational behavior evoked by electrical stimulation in the lateral hypothalamus. Rats were tested daily for electrical stimulation-induced rotational behavior (ESRB) for 5 days, and then given an injection of 6-hydroxydopamine (6-OHDA) or saline into the ipsilateral substantia nigra. The nearly total depletion of striatal DA (greater than 96%) completely abolished contraversive ESRB and resulted in the appearance of ipsiversive ESRB. Partial DA depletion (less than 95%) had no effect on contraversive ESRB. In animals with a partial DA depletion subsequent treatment with a low dose of alpha-methyl-p-tyrosine (40 mg/kg) attenuated contraversive ESRB, while having no effect on control animals, or the ipsiversive turning in animals with greater than 96% DA depletion. We conclude that the nigrostriatal DA system is necessary for contraversive rotational behavior evoked by lateral hypothalamic stimulation, but that only a small percentage of DA fibers are required to maintain apparently 'normal' function--at least as indicated by contraversive ESRB.

Animals↗
PubMed1985

Formation of a fluorescent glucocorticoid receptor-steroid complex in HTC cell cytosol.

An intensely fluorescent rhodamine derivative of dexamethasone (i.e. Dex-C2-Rho) was synthesized. Dex-C2-Rho possessed high affinity for HTC cell glucocorticoid receptors in cell-free systems. Whole cell activity and receptor affinity of Dex-C2-Rho were both much lower, apparently due to problems with cell permeability and/or metabolism. A specific, fluorescent receptor-steroid complex at concentrations as low as 1 X 10(-9) M could readily be observed with crude HTC cell receptors after removal of the free Dex-C2-Rho. This appears to be the first report of a fluorescent glucocorticoid receptor-steroid complex.

Animals↗
PubMed1985

Sensitization of rotational behavior produced by a single exposure to cocaine.

In rats with a unilateral 6-OHDA lesion of the substantia nigra a single exposure to cocaine significantly enhanced the ipsiversive rotational behavior produced by a second injection given one week later. It is concluded that it is not necessary to repeatedly administer psychomotor stimulant drugs to produce long-lasting changes in brain and behavior.

Animals↗
PubMed1985

Immediate effects of cigarette smoking on cardiorespiratory responses to exercise.

To determine the acute action of cigarette smoking on cardiorespiratory function under stress, the immediate effects of cigarette smoking on the ventilatory, gas exchange, and cardiovascular responses to exercise were studied in nine healthy male subjects. Each subject performed an incremental exercise test to exhaustion on two separate days, one without smoking (control) and one after smoking 3 cigarettes/h for 5 h. The order of the two tests was randomized. Arterial blood gases and pH were measured during rest and all levels of exercise; CO blood levels confirmed the absorption of cigarette smoke. In addition, minute ventilation (VE), end-tidal PCO2 and PO2, O2 uptake (VO2), CO2 production, directly measured blood pressure, electrocardiogram, and heart rate (HR) were recorded every 30 s. The dead space-to-tidal volume ratio (VD/VT), maximal aerobic capacity (VO2max), and anaerobic threshold (AT) were determined from the gas exchange data. Cigarette smoking resulted in a significantly lower VO2max, AT, and VO2/HR (O2 pulse) and a significantly higher HR, pulse-pressure product, and pulse pressure (P less than 0.05) compared with the control. Additionally, a trend toward a higher VD/VT and arterial-end-tidal PCO2 difference was found during exercise after smoking. We conclude that cigarette smoking causes immediate detrimental effects on cardiovascular function during exercise, including tachycardia, increased pulse-pressure product, and impaired O2 delivery. The acute effects on respiratory function were less striking and primarily limited to abnormalities reflecting ventilation-perfusion mismatching.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Cardiovascular investigations of an endogenous digoxin-like factor.

A circulating factor with digoxin immunoreactivity has been demonstrated. Elevated levels of this substance appear to be present after volume expansion and salt loading, and in some forms of hypertension. The potentially causative role for this factor in hypertension can be demonstrated by the normalization of blood pressure after antidigoxin antibody infusions in low-renin and sodium-dependent hypertension. The possibility that renal excretory defects may be the initiating event to elevate endogenous digoxin is suggested by studies with normotensive humans and monkeys with renal disease. In the latter case cardiovascular deficits were noted that were analogous to those detected in renal hypertensive monkeys with elevated endogenous digoxin. Considered together, these results suggest the existence of a natriuretic and hypertensive substance that plays a role in body fluid homeostasis and blood pressure regulation.

Animals↗
PubMed1984

Striatal dopamine release stimulated by amphetamine or potassium: influence of ovarian hormones and the light-dark cycle.

The release of endogenous dopamine (DA) from rat striatal tissue was studied in an in vitro superfusion system following hormonal manipulations in vivo. Progesterone treatment in estrogen-primed ovariectomized female rats potentiated DA release stimulated either by amphetamine or potassium (K+). In addition, the amount of striatal DA released in response to K+-stimulation was influenced by the light-dark cycle. We conclude that striatal DA release is modulated by ovarian hormones, and suggest that ovarian hormone modulation of presynaptic striatal DA activity may contribute to well-known estrous cycle dependent variations in some non-reproductive behaviors.

Animals↗
PubMed1984

Behavioral sensitization: characterization of enduring changes in rotational behavior produced by intermittent injections of amphetamine in male and female rats.

Factors influencing the behavioral sensitization ("reverse tolerance") produced by intermittent amphetamine (AMPH) injections were studied by quantifying rotational behavior in rats that had a unilateral 6-hydroxy-dopamine lesion of the substantia nigra. The results indicate that: a single injection of a low dose of AMPH enhances rotational behavior induced by a second injection of AMPH for up to 12 weeks; multiple, weekly injections of AMPH produce a progressive enhancement in rotational behavior, over-and-above that produced by a single injection; female rats show more robust sensitization than males following single or multiple injections of AMPH; this sex difference may be due to the suppression of sensitization by an androgen, because removal of testicular hormones potentiates sensitization; the long-lasting sensitization of rotational behavior produced by infrequent injections of AMPH is not due to drug-environment conditioning effects, but perhaps to a persistent AMPH-induced change(s) in brain catecholamine systems; and a simple change in DA receptors is probably not involved, because the sensitization produced by infrequent injections of AMPH does not influence the rotation produced by a subsequent injection of apomorphine. The results illustrate an intriguing example of neuroplasticity that may have clinical relevance.

Amphetamine↗