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E Castañeda

Publications and source records attributed to E Castañeda.

At least 55 records · Page 3Linked to original sources
PubMed1993

Effects of cortical serotonin depletion induced by 3,4-methylenedioxymethamphetamine (MDMA) on behavior, before and after additional cholinergic blockade.

Repeated treatment with high doses of 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") produces a long-lasting depletion of brain serotonin, presumably because of the degeneration of serotonin axon terminals. However, very little is known about the long-term behavioral consequences of MDMA neurotoxicity. The experiments reported here were designed to evaluate the effects of MDMA neurotoxicity on a number of behavioral tests known to be sensitive to neocortical and hippocampal damage. Also, the effect of additional cholinergic blockade in MDMA-pretreated rats was evaluated because loss of both the serotonergic and cholinergic inputs to the cortex produces a functional decortication and a behavioral syndrome reminiscent of human global dementia. Partial depletion of neocortical serotonin (72.6%) did not produce deficits on a variety of behavioral tests, including a place navigation learning-set task, skilled forelimb use, or the ability to make complex judgements regarding the stimulus properties of food in a foraging situation, and neither did additional cholinergic blockade. MDMA-pretreated rats had a mild impairment in rapidly developing an efficient search strategy in the place navigation task, but once the goal was located, MDMA pretreated rats performed at control levels and showed no deficits in memory for spatial location. It is concluded that the extent of serotonergic denervation produced by MDMA is not sufficient to produce marked and lasting behavioral deficits, possibly because of neurocompensatory changes in the remaining serotonin terminals.

3,4-Methylenedioxyamphetamine↗
PubMed1992

Do forebrain structures compete for behavioral expression? Evidence from amphetamine-induced behavior, microdialysis, and caudate-accumbens lesions in medial frontal cortex damaged rats.

The neurochemical basis of behavioral changes following medial frontal cortex damage were investigated. Experiment 1 examined locomotion in response to D-amphetamine (1.5 and 5 mg/kg) in rats that had received bilateral aspirative lesions of the medial frontal cortex alone or in combination with 6-hydroxydopamine (6-OHDA) lesions of the nucleus accumbens or caudate-putamen. Relative to controls, medial frontal cortex rats were initially hypoactive (day 1 postoperative) but rapidly became hyperactive (days 5-15 postoperative). Locomotor-time profiles and stereotypy ratings showed that amphetamine produced a selective enhancement of locomotion at the expense of stereotyped behavior. Nucleus accumbens lesions blocked the locomotion but enhanced stereotyped behavior in the medial frontal cortex damaged rats, suggesting that amphetamine-enhanced locomotion is dependent upon the integrity of the nucleus accumbens. In Experiment 2, intracerebral microdialysis was used to examine whether alterations in dopamine (DA) or monoamine metabolites in the nucleus accumbens or caudate-putamen accompanied the lesion-induced changes in locomotion. There were no differences in extracellular DA or monoamine levels between control rats and medial frontal cortex rats when tested on day 1 or day 15 postsurgery, either when they were at rest, while they walked on a motor-driven belt, or after amphetamine treatment. Therefore, it seems unlikely that changes in amphetamine-induced locomotion following medial frontal cortex lesions are related to underlying modifications in dopaminergic activity in the nucleus accumbens. It is suggested that neural structures compete for behavioral expression and that postlesion behavioral alterations reveal the competitive advantage of remaining intact neural systems.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Dopamine and skilled limb use in the rat: more severe bilateral impairments follow substantia nigra than sensorimotor cortex 6-hydroxydopamine injection.

The experiments examined the suggestion that the dopaminergic (DA) projection to the motor cortex are involved in the motor impairments that follow complete hemitelencephalic DA depletions. The neurotoxin, 6-hydroxydopamine (6-OHDA), was injected unilaterally into the sensorimotor cortex (MCtx), the ventral tegmental area (VTA), or into the substantia nigra pars compacta (SN) of rats trained to reach for food with either forelimb. The SN injections produced large (greater than 95%) unilateral striatal dopamine (DA) depletions and severe bilateral impairments in limb use. VTA and MCtx injections did not produce impairments in limb use or severe depletions of cortical DA. An effective test of the contribution of cortical DA to skilled limb use must await a more effective technique for producing selective cortical DA depletion. Nevertheless, the results suggest that the severe impairments of skilled forelimb use that follow hemitelencephalic DA depletions may stem primarily from depletion of the nigrostriatal DA projection.

Animals↗
PubMed1992

Recovery from lateralized neocortical damage: dissociation between amphetamine-induced asymmetry in behavior and striatal dopamine neurotransmission in vivo.

It has been hypothesized that neocortical damage is accompanied by secondary changes in other brain areas (the shock or diaschisis of von Monakow), which contributes to initial non-specific behavioral depression. The relation between behavioral changes and dopamine (DA), serotonin (5-HT), and their metabolites, measured with intracerebral microdialysis in freely moving rats and by tissue assay postmortem, was examined during postsurgical recovery from unilateral hemidecortications. Rats were tested for rotational asymmetry and extracellular concentration of DA was measured both during rest and after amphetamine (1.5 mg/kg). It was found that: (1) during the first few postsurgical days the hemidecorticate rats rotated ipsilateral to their lesions after amphetamine but thereafter on tests given up to 121 days postsurgery concentration of DA or its metabolites at any time after surgery; (3) the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) was elevated acutely for a few days following surgery; (4) during the first 3 postoperative days, both baseline extracellular 3,4-dihydroxyphenylacetic acid (DOPAC) and amphetamine-induced DA release were significantly elevated bilaterally. These findings demonstrate that the acute behavioral asymmetry in rotation produced by hemidecortication is not related to unilateral changes in striatal DA activity and its metabolites. Thus, the behavioral asymmetries might be related to other striatal changes (i.e. 5-HIAA) or other damage, such as to the corticospinal projections of the lesioned hemisphere. Nevertheless, unilateral lesions did produce acute bilateral increases in DA levels, which may be a correlate of generalized neural shock produced by the lesion.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

THC does not affect striatal dopamine release: microdialysis in freely moving rats.

The hypothesis that cannabinoids potentiate the motor effects of neuroleptics and produce their abuse potential by stimulating dopaminergic activity was tested by measuring the ability of THC to increase extracellular dopamine concentrations. Male Long-Evans rats were implanted with guide cannulae for the striatum or nucleus accumbens. Fifteen hours prior to testing, removable microdialysis probes were inserted through the guide cannulae. Dialysis samples were collected during resting baseline, after 1.0 mg/kg, 10 mg/kg THC, or vehicle of olive oil with 5% ETOH (by gavage) followed by amphetamine (1.5 mg/kg) or fluphenazine (0.3 mg/kg). THC produced no change in the extracellular concentrations of DA, DOPAC, and HVA, nor in 5-HIAA. THC also had no effect on the enhancement of extracellular DA produced by amphetamine nor on the transient increase in DA, DOPAC, and HVA produced by fluphenazine. There were also no behavioral differences between groups during any of these treatments.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Dopamine depletion in neonatal rats: effects on behavior and striatal dopamine release assessed by intracerebral microdialysis during adulthood.

Rats depleted of dopamine (DA) by intraventricular 6-hydroxydopamine (6-OHDA) in infancy show behavioral impairments as adults, but their basic sensory-motor functions and feeding abilities are intact; at least relative to the pronounced deficits seen in rats given similar treatment in adulthood. Here we investigate whether presynaptic changes culminating in enhanced DA release are present in adult rats that received neonatal damage, and whether these are of a sufficient magnitude to contribute to the sparing of function. We used microdialysis in rats during the resting state, walking on a treadmill, and after a systemic injection of amphetamine. It was found that neonatal 6-OHDA produced a nearly complete (less than 1% of control) depletion of DA in postmortem tissue, but this was not accompanied by a comparable decline in the basal extracellular concentrations of DA, which were only reduced by 12-54% of control values. In contrast, the extracellular concentrations of DA metabolites were greatly reduced, reflecting the post-mortem tissue concentrations of DA. Nevertheless, neonatally depleted animals were markedly deficient in their ability to respond to an amphetamine challenge, both behaviorally and in their ability to further increase DA release. Thus, following neonatal DA depletion there appear to be extensive changes in the few remaining DA terminals that are sufficient to maintain relatively high extracellular (and presumably synaptic) concentrations of DA during the resting state, but the capacity of the remaining DA neurons to respond to increased demand is very limited. This presynaptic compensatory response may play a role in the sparing of behavioral function seen following neonatal damage.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Compensatory changes in striatal dopamine neurons following recovery from injury induced by 6-OHDA or methamphetamine: a review of evidence from microdialysis studies.

This paper presents evidence from microdialysis experiments that three different behavioural outcomes of depletion of striatal dopamine (DA) by either 6-hydroxydopamine or methamphetamine (sparing of function, recovery of function, and loss of function) may be related to differences in the ability of residual DA neurons to maintain extracellular concentrations of DA. It is shown that when up to 80% of the mesostriatal DA system is destroyed, the remaining DA terminals maintain normal extracellular dopamine concentrations. Following a lesion in the 80-95% range, most animals maintain a relatively normal extracellular concentration of DA, but the ability to respond to increased demand is reduced in some animals. When over 95% of the normal DA input to the striatum is destroyed, there is a sharp drop in the extracellular concentration of DA and a nearly complete loss in the ability to increase DA release upon demand. Thus, this new method of sampling extracellular DA and its metabolites in freely moving animals provides insights into the behavioural capacities of animals and into the neural mechanisms that underlie recovery of function following brain damage.

Animals↗
PubMed1990

Changes in striatal dopamine neurotransmission assessed with microdialysis following recovery from a bilateral 6-OHDA lesion: variation as a function of lesion size.

Intracerebral microdialysis was used to measure the extracellular concentration of striatal dopamine (DA) and its metabolites in freely moving rats depleted of DA by the bilateral infusion of 6-hydroxydopamine into the substantia nigra approximately 1 month earlier. It was found that the basal extracellular concentration of DA remained within the same range as seen in control animals until the size of the lesion exceeded 80% (estimated by the postmortem tissue concentration of DA). In animals with an 80-95% lesion there was only a modest decrease in basal extracellular DA, but as lesion size exceeded 95% there was a marked drop in the basal extracellular concentration of DA. In contrast, the basal extracellular concentration of the DA metabolites showed a more steady decline as a function of lesion size. To determine the ability of the residual population of DA terminals to further increase DA release upon increased demand, animals were given a challenge injection of 1.5 mg/kg of d-amphetamine. Amphetamine-evoked DA release remained within the control range until lesion size exceeded 95%. These results provide direct confirmation for the hypothesis that following recovery from partial bilateral damage to the nigrostriatal DA system in adulthood, there are presynaptic compensatory changes in the remaining population of DA neurons sufficient to "normalize" the extracellular concentration of striatal DA. It is suggested that this normalization of extracellular DA is responsible for the sparing of function seen following the loss of up to 80% of the DA innervation to the striatum and contributes to the recovery of function seen after even more extensive damage (80-95%).(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
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↗
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

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↗
PubMed1984

A simple in vitro technique to measure the release of endogenous dopamine and dihydroxyphenylacetic acid from striatal tissue using high performance liquid chromatography with electrochemical detection.

An easily constructed, inexpensive and simple system is described for the superfusion of neural tissue. To characterize the system, the dynamics of endogenous dopamine and dihydroxyphenylacetic acid release from striatal tissue were studied before and after exposure to potassium, amphetamine or cocaine.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Chronic murine paracoccidioidomycosis: effect of ketoconazole on clearance of Paracoccidioides brasiliensis and immune response.

In a murine model of chronic pulmonary and disseminated paracoccidioidomycosis, ketoconazole (100 mg kg-1 in 0.3% agar) given by gavage twice daily for 1 or 2 months enabled all mice to clear disseminated Paracoccidioides brasiliensis from the spleen. Clearance of P. brasiliensis from the lungs was more difficult, and was achieved in 60% of the mice treated for 2 months. Sera from agar-treated control mice at days 77 and 103 post-infection demonstrated precipitating antibodies to P. brasiliensis antigens, but sera from ketoconazole-treated mice were precipitin-negative, indicating a favorable prognosis. Delayed hypersensitivity reactions to P. brasiliensis antigens in ketoconazole-treated mice were not significantly greater than in controls; consequently this test correlated less well with response than levels of serum antibody. This is the first use of this animal model of paracoccidioidomycosis to study the effect of antifungal drug protocols on the resolution of the disease. It also demonstrates the utility of this model in addressing clinically relevant questions about this disease and its treatment.

Animals↗
PubMed1980

An automated method for studying stereotyped gnawing.

Stereotyped behavior in rats, consisting of compulsive, repetitive sniffing and gnawing, caused by high doses of amphetamine-like psychostimulants, may serve as an animal model for psychosis. Previous methods for measuring behavioral stereotypies of this kind have required continuous observation and rating of the behaviors or semiquantitative techniques that fail to produce a continuous record of the behaviors. The present paper describes a simple automated method that provides a continuous quantitative record of the specific gnawing behavior induced in rats by methylphenidate, an amphetamine-like psychostimulant. The apparatus described and the test procedures developed are compatible with a wide variety of common counters and recorders.

Animals↗