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J B Becker

Publications and source records attributed to J B Becker.

At least 55 records · Page 3Linked to original sources
PubMed1990

Adrenal medulla graft induced recovery of function in an animal model of Parkinson's disease: possible mechanisms of action.

Following unilateral dopamine (DA) denervation of the striatum in animals, there is an asymmetry in the striatal DA system. Animals with such denervations will rotate vigorously when given dopaminergic drugs. Adrenal medulla grafts placed in the lateral ventricle adjacent to a DA-denervated striatum decrease rotational behaviour induced by DA receptor agonists or DA-releasing agents. This discussion reviews research on the use of adrenal medulla grafts to reverse behavioural deficits following DA-denervation of the striatum. Results from basic animal research and from the application of the procedure to patients with Parkinson's disease suggests that at least three different fundamental processes may mediate the functional effects of adrenal medulla grafts: (a) Adrenal medulla grafts may induce changes in the blood-brain barrier; (b) adrenal medulla grafts may induce an increase in serum DA; and (c) adrenal medulla grafts may have a trophic effect on the host brain. Hypotheses are proposed to explain the behavioural effects of adrenal medulla grafts in light of the processes that are thought to mediate their effects.

Adrenal Medulla↗
PubMed1990

Transient hypoxia alters striatal catecholamine metabolism in immature brain: an in vivo microdialysis study.

Microdialysis probes were inserted bilaterally into the striatum of 7-day-old rat pups (n = 30) to examine extracellular fluid levels of dopamine, its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA). The dialysis samples were assayed by HPLC with electrochemical detection. Baseline levels, measured after a 2-h stabilization period, were as follows: dopamine, not detected; DOPAC, 617 +/- 33 fmol/min; HVA, 974 +/- 42 fmol/min; and 5-HIAA, 276 +/- 15 fmol/min. After a 40-min baseline sampling period, 12 animals were exposed to 8% oxygen for 120 min. Hypoxia produced marked reductions in the striatal extracellular fluid levels of both dopamine metabolites (p less than 0.001 by analysis of variance) and a more gradual and less prominent reduction in 5-HIAA levels (p less than 0.02 by analysis of variance), compared with controls (n = 12) sampled in room air. In the first hour after hypoxia, DOPAC and HVA levels rose quickly, whereas 5-HIAA levels remained suppressed. The magnitude of depolarization-evoked release of dopamine (elicited by infusion of potassium or veratrine through the microdialysis probes for 20 min) was evaluated in control and hypoxic animals. Depolarization-evoked dopamine efflux was considerably higher in hypoxic pups than in controls: hypoxic (n = 7), 257 +/- 32 fmol/min; control (n = 12), 75 +/- 14 fmol/min (p less than 0.001 by analysis of variance). These data demonstrate that a brief exposure to moderate hypoxia markedly disrupts striatal catecholamine metabolism in the immature rodent brain.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Estrous cycle-dependent variation in amphetamine-induced behaviors and striatal dopamine release assessed with microdialysis.

Estrous cycle-dependent variation in amphetamine (AMPH)-stimulated behaviors and striatal dopamine (DA) release were determined for freely moving rats undergoing intracerebral microdialysis. There was greater AMPH-stimulated striatal DA release in the striatum of rats in estrus, during the period from 20 min to 100 min post-AMPH, compared with the response of rats in diestrus (P less than 0.05). Animals in estrus also showed less general activity and greater intensity of stereotyped behaviors than did animals in diestrus (P less than 0.05). Independent experiments examining estrous cycle-dependent differences in AMPH-stimulated striatal DA release in vitro also found that AMPH-stimulated striatal DA release was greater on estrus than on diestrus (P less than 0.05). Thus, striatal DA release and behaviors induced by AMPH are modulated by ovarian hormones. The heightened responsiveness to AMPH during estrus suggests that estrogen and/or progesterone potentiate the striatal DA response to AMPH.

Animals↗
PubMed1989

An endogenous 'hypertensive factor' enhances the voltage-dependent calcium current.

The effects of an immunoaffinity-purified putative endogenous hypertensive factor (HF) on voltage-dependent calcium current in frog cardiac myocytes were assessed. In 9 out of 10 cells, HF reversibly increased the peak amplitude of the calcium current. HF increased peak calcium current density at -5 mV from a control level of 1.8 +/- 1.3 pA/pF (mean +/- SD) to 4.4 +/- 2.0 pA/pF. HF shifted the peak of the calcium current-voltage relationship in the hyperpolarizing direction. HF shifted the voltage dependence of the inactivation of the calcium current to more negative potentials with prepulses from -80 to 0 mV, but the inactivation was not affected with prepulses more positive than 0 mV. Modulation of the voltage-dependent calcium current by HF may be the mechanism underlying its pressor effects.

Action Potentials↗
PubMed1988

Adrenal medulla grafts enhance functional activity of the striatal dopamine system following substantia nigra lesions.

Adrenal medulla grafts in the lateral ventricle reduce the behavioral manifestations of striatal dopamine depletion in an animal model of Parkinson's disease. Using microdialysis in freely moving rats, the present experiments determined that dopamine was not detectable in cerebrospinal fluid (CSF). However, adrenal medulla grafts were associated with an increase in dopamine turnover and amphetamine-stimulated striatal dopamine release was increased in animals with behaviorally effective adrenal medulla grafts. Therefore, adrenal medulla grafts increase striatal dopamine activity without an appreciable release of dopamine into the CSF. Adrenal medulla grafts also increased serum dopamine concentrations, and the increase in serum dopamine was directly correlated with the behavioral efficacy of the grafts. We suggest that dopamine, produced by adrenal medulla grafts, may gain access to the striatum via the blood supply and then leak out into the host striatum through permeable blood vessels adjacent to the graft. Through this mechanism, adrenal medulla grafts may increase functional dopaminergic activity in the striatum. These results may be important for understanding how autografts of adrenal medulla cells produce a putative alleviation of the symptoms of Parkinson's disease.

Adrenal Cortex↗
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↗
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

The influence of estrous cycle and intrastriatal estradiol on sensorimotor performance in the female rat.

The influence of estrous cycle and intrastriatal implants of 17 beta-estradiol (17 beta-estradiol). 17 alpha-estradiol (17 alpha-estradiol) or cholesterol on the number of footfaults made by female rats traversing a narrow suspended beam was investigated. Female rats made fewer footfaults on estrus than on other days of the cycle. This was true when testing occurred during either the light or dark phase of the light:dark cycle. Intrastriatal implants of 30% 17 beta-estradiol for 6 hours resulted in a significant improvement in sensorimotor performance as soon as 4 hours after hormone implant and persisting for days. In contrast, intrastriatal implants of either 30% 17 alpha-estradiol or cholesterol had no influence on performance. The extent of hormone diffusion away from the implant cannula was minimal, and the resulting concentration of 17 beta-estradiol in the striatum was less than 10 pg/mg. It is concluded that estradiol has a direct, stereospecific effect in the striatum that influences performance of a skilled motor act in the female rat.

Animals↗
PubMed1986

The influence of estrogen on nigrostriatal dopamine activity: behavioral and neurochemical evidence for both pre- and postsynaptic components.

The results of 3 experiments examining the influence of estrogen on the nigrostriatal dopamine (DA) system are reported. In two experiments the influence of hormonal manipulations on amphetamine (AMPH)-induced rotational behavior was investigated using rats with unilateral 6-hydroxydopamine lesions of the substantia nigra. It was found that: (1) female rats in estrus make more rotations than ovariectomized (OVX) rats; and (2) estrogen treatment (5 micrograms estradiol benzoate, daily for 4 days) in OVX rats enhances AMPH-induced rotational behavior 4 h and 4 days after estrogen treatment. During the intervening period, at 24 h after cessation of estrogen treatment, control and hormone-treated animals did not differ. In a third experiment, the effect of estrogen treatment on the release of endogenous DA from striatal tissue slices in superfusion was examined. Estrogen enhanced AMPH-stimulated striatal DA release 4 h after the last treatment relative to OVX controls. However, 24 h and 4 days after estrogen treatment DA release had returned to control levels. It is suggested that estrogen has an immediate potentiating effect on striatal DA release, and this may be responsible for the increased behavioral response to AMPH 4 h after estrogen treatment. The previously demonstrated increase in postsynaptic striatal DA receptors may be responsible for the second increase in AMPH-induced rotational behavior, that occurs 4 days after estrogen treatment.

Animals↗
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

Effects of neonatal forebrain noradrenaline depletion on recovery from brain damage: performance on a spatial navigation task as a function of age of surgery and postsurgical housing.

The experiments examined the contributions of forebrain noradrenaline and environmental enrichment to recovery of place navigation ability in rats after hemidecortication in infancy or adulthood. Noradrenaline depletion did not affect recovery from neonatal hemidecortication, although the early hemidecortications did allow sparing of function relative to adult operates. Noradrenaline depletion also failed to attenuate the positive effects of enriched housing on otherwise normal rats. Noradrenaline depletion did retard recovery of adult hemidecorticate rats housed in standard laboratory cages, but it did not retard recovery of adult hemidecorticate rats housed in enriched environments. The results suggest that noradrenaline is importantly involved in enhancing recovery from brain damage when other sources of compensation (e.g., neonatal injury, enriched environment) are absent.

Animals↗
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↗
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↗