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Biomedical subjects

E Castañeda

Publications and source records attributed to E Castañeda.

At least 19 recordsLinked to original sources
PubMed1996

Effects of amphetamine and 6-hydroxydopamine lesions on reserpine-induced oral dyskinesia.

The present study examined whether reserpine-induced oral dyskinesia is mediated by release of residual endogenous dopamine. Amphetamine produced a dose-dependent change in reserpine-induced oral dyskinesia in which the response was exacerbated by 0.6 mg/kg amphetamine and inhibited by 1 mg/kg. The latter dose also produced stereotypy that may have interfered with expression of reserpine-induced oral dyskinesia. Nigrostriatal 6-hydroxydopamine lesions attenuated expression of reserpine-induced oral dyskinesia. These lesions did not reduce locomotor activity, however, indicating that the attenuation of reserpine-induced oral dyskinesia was not due to a general depressant effect of the lesions on motor behavior. These results suggest that increasing dopamine release by administration of amphetamine exacerbates reserpine-induced oral dyskinesia, whereas decreasing the amount of releasable dopamine in the striatum by 6-hydroxydopamine lesions attenuates reserpine-induced oral dyskinsia. These findings may have implications for understanding tardive dyskinesia and L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia.

Adrenergic Agents↗
PubMed1996

Changes in behavior and monoamine levels in microdialysate from dorsal striatum after 6-OHDA infusions into ventral striatum.

Long-Evans rats received bilateral 6-hydroxydopamine infusions into the nucleus accumbens and were tested immediately (1 and 2 days) or after a recovery period (14 and 15 days) for changes in extracellular levels of dorsal striatal monoamines using in vivo microdialysis. Compared to controls, the monoamine metabolites 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid were generally enhanced when tested immediately after 6-hydroxydopamine treatment, including spontaneous levels and those following depolarizing infusions of potassium (60 mM, 20 min) through the microdialysis probes. Following 2 weeks recovery, dopamine metabolite levels were depressed and the serotonin metabolite levels remained enhanced. D-Amphetamine sulfate (1.5 mg/kg, SC) stimulated dopamine overflow was enhanced 2 days after 6-hydroxydopamine administration, but not after 2 weeks recovery. In contrast, potassium increased dopamine overflow to the same extent as control animals regardless of recovery period following 6-hydroxydopamine. The immediate changes in striatal monoamine activity were accompanied by a potentiation of amphetamine-induced stereotyped behaviors. We suggest that transient presynaptic changes within the dorsal striatum following disruption of the ventral striatum may mediate some general aspects of loss and recovery of behavior related to the time course of 6-hydroxydopamine neurotoxicity.

Adrenergic Uptake Inhibitors↗
PubMed1996

Dopamine overflow in the nucleus accumbens during extinction and reinstatement of cocaine self-administration behavior.

Both cocaine and cocaine-associated stimuli can reinstate extinguished self-administration behavior in animals. It has been suggested that reinstatement of drug-seeking behavior may be mediated by enhanced dopamine (DA) neurotransmission. To examine this hypothesis, DA overflow was measured in the nucleus accumbens (NAc) of rats during both extinction and cocaine-induced reinstatement of self-administration behavior. Rats were either allowed to self-administer cocaine for 3 hours daily for 14 days, or they received yoked administration of saline. A stimulus light above the lever was illuminated during drug delivery. Baseline DA overflow was measured in the NAc, using in vivo microdialysis 7 to 8 days after the last self-administration session. The rats were then placed into the operant chambers and allowed to respond in extinction for 90 minutes, during which responses resulted in presentation of the stimulus light. The rats then received a cocaine injection that reinstated self-administration behavior. Contrary to our hypothesis, cocaine-experienced animals exhibited less DA overflow in the NAc relative to controls during both extinction and reinstatement.

Animals↗
PubMed1995

Safety and immunogenicity of oral killed whole cell recombinant B subunit cholera vaccine in Barranquilla, Colombia.

In January and February 1992, an assessment was conducted of the safety and immunogenicity of two doses of a new oral cholera vaccine prepared from the recombinant B subunit of the toxin and from killed whole cells (rBS/WC) in 1,165 individuals between the ages of 12 months and 64 years in Barranquilla, Colombia. This was a randomized, double-blind placebo-controlled study. Participants received two doses of either the vaccine or a placebo (killed Escherichia coli K12) over a two-week interval. Few symptoms were detected during the three days following administration of the initial dose and even fewer following the second. Sera obtained upon administration of the first dose and two weeks after administration of the second were tested for Vibrio cholerae 01 Inaba vibriocidal antibodies and antitoxins. Geometric mean titers (GMT) of vibriocidal antibodies were found to increase two-fold in subjects receiving the vaccine. In the paired samples taken from vaccinated subjects, two-fold or greater increases were observed in 44% and four-fold or greater increases were observed in 34%, as compared to similar increases in 9.2% and 2.2% of the sera taken from those receiving the placebo (P < 0.05). The GMTs of IgG and IgA antitoxins, as determined by ELISA, increased by factors of 4 and 3.2, respectively, in those receiving the vaccine, as compared to factors of 1.1 and 1.1 in those given the placebo (P < 0.001 for IgG, P < 0.01 for IgA). Approximately 80% of the paired samples from the vaccinated group showed an increase of both IgG and IgA antitoxins > or = 1.5, as compared to only about 20% of those in the placebo group (P < 0.000001). Belonging to the O blood group did not significantly affect the immune response. Children under age four tended to show a weaker vibriocidal antibody response and a stronger antitoxin response than older subjects. The two doses of oral vaccine were found to be safe and without attributable side-effects. The vibriocidal antibody and antitoxin responses were similar to those obtained previously with the conventional oral killed whole cell B subunit cholera vaccine.

Administration, Oral↗
PubMed1994

Making two movements at once: impairments of movement, posture, and their integration underlie the adult skilled reaching deficit of neonatally dopamine-depleted rats.

Adult rats depleted bilaterally of dopamine in infancy display a profound impairment in skilled forelimb use in reaching for food. This impairment was investigated using end-point measures of reaching success, movement analysis, and kinematic measures. The rats made few successful reaches in either an easy or a difficult reaching test. Their reaches were characterized by many attempts in which trajectories of the limb were irregular and the movements were slow. Their lack of success was related in part to an impairment in making component movements of the reach, including aiming, pronating, grasping, and supinating the paw and in releasing the food pellet. It was also related to an inability to adjust posture as the limb was voluntarily moved toward the food. The results are consistent with the hypotheses that the basal ganglia, including its dopamine innervation, is important for enabling voluntary movements and postural adjustments and perhaps also the simultaneous performance of two movements at the same time.

Aging↗
PubMed1994

Dose-dependent differences in the development of reserpine-induced oral dyskinesia in rats: support for a model of tardive dyskinesia.

Rats treated with reserpine develop spontaneous orofacial dyskinesia that has features similar to tardive dyskinesia (TD) in humans. In contrast to TD, however, reserpine-induced oral dyskinesia develops rapidly reaching a maximal level within 3 days at a dose of 1 mg/kg per day. The present study examined whether rats administered lower doses of reserpine would develop the oral dyskinesia at a slower rate, similar to the protracted development of TD. Rats were administered 0, 0.01, 0.05, 0.1, or 1.0 mg/kg reserpine subcutaneously every other day for 100 days. Oral dyskinesia was measured by recording the incidence of tongue protrusions for 30 min on days 1, 4, 10, 20, 40, 60, and 100. The time course of the development of reserpine-induced oral dyskinesia varied dose-dependently. The response was evident within 4 days at 1 mg/kg, within 20 days at 0.1 mg/kg, within 60 days at 0.05 mg/kg, and was not evident at 0.01 mg/kg at any time during the 100 days of treatment. The protracted development of reserpine-induced oral dyskinesia at the lower doses is consistent with TD. Doses of reserpine that produced an increase in tongue protrusions also produced a 90-95% depletion of dopamine and an increase in the ratio of dopamine metabolites to dopamine in the caudate-putamen. The disruption of dopamine neurotransmission may be involved in development of the oral dyskinesia. Furthermore, it is suggested that the 1 mg/kg dose of reserpine may induce neurochemical changes similar to that produced by long-term neuroleptic treatment, but at an accelerated rate, thereby providing a new efficient model of TD.

Animals↗
PubMed1994

Kinetics of the vibriocidal antibody response to live oral cholera vaccines.

The best correlate of protection against cholera is the level of serum vibriocidal antibodies, which are primarily directed against the O antigen of Vibrio cholerae O1 and lyse V. cholerae in the presence of complement. We established the timing of peak vibriocidal antibody response using sera from safety/immunogenicity studies of live oral cholera vaccines CVD 103-HgR, CVD 103-HgR2 and CVD 110 among immunologically naive North Americans and Colombians. The serum reciprocal vibriocidal antibody titre was consistently higher 10 days postimmunization than on either day 7 or day 14. This study suggests that recent phase 2 studies of CVD 103-HgR may have underestimated the peak vibriocidal titre by collecting serum on days 7-8 rather than on day 10; future studies of live oral cholera vaccines should take these results into account to obtain the best measurement of peak immunological responses. Because of the rapid drop in vibriocidal antibody titres about 2 weeks after immunization, care must be exercised in comparing immunogenicity of different vaccine candidates, formulations, dosage levels and immunization schedules.

Administration, Oral↗
PubMed1994

Skilled reaching deficits in unilateral dopamine-depleted rats: impairments in movement and posture and compensatory adjustments.

Rats receiving unilateral dopamine (DA) depletions have bilateral deficits in using the forelimbs for skilled reaching. These impairments were investigated using end-point, video, and kinematic measures. Control rats and groups of rats with > 98% unilateral depletions (confirmed by tissue, apomorphine, and amphetamine assay), produced by 6-hydroxydopamine (6-OHDA) injected into the nigrostriatal bundle, were tested for 100 d on two reaching tasks. One depleted group used the contralateral-to-lesion (bad), and the other the ipsilateral-to-lesion (good), limb. Rats using their bad limb made few successful reaches and had dysfunctions in aiming, pronating, and supinating, and in using the digits to grasp and release food. Rats using the good limb were initially impaired, but improved, and could make these movements. Neither depleted group was able to use their bad limbs to assist actively the postural changes required for reaching. Thus, they did not use the diagonal supporting pattern (the nonreaching forelimb and diagonal hind limb) from which control rats initiated reaching. The group using their bad limb initiated reaching from a base of support distributed on the ipsilateral-to-lesion limbs, while the group using their good limb initiated reaching from a base of support centered on the ipsilateral rear limb. The impairments in making voluntary movements and postural adjustments with the bad limbs and the behavioral changes introduced by the compensatory dependency on good limbs account for the bilateral deficits in skilled movements. The results show that DA is required for skilled movements and postural adjustments and demonstrate that behavioral compensation can contribute to recovery.

Adaptation, Physiological↗
PubMed1993

The role of the striatum in organizing sequences of play fighting in neonatally dopamine-depleted rats.

Juvenile rats sustaining dopamine depletions by intraventricular injections of 6-hydroxydopamine (6-OHDA) as neonates were used to study the role of the striatum in controlling play fighting. As juveniles, the rats exhibited all the behavior elements typical of play fighting. However, they were more likely to use defensive tactics that shortened the playful contact between partners; and when contacting the partner, they were more likely to switch to other behaviors, such as allogrooming and sexual mounting, rather than continue with the play sequence. It is suggested here that the striatum is important for maintaining sequential organization of play fighting.

Aggression↗
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↗