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J Laguna

Publications and source records attributed to J Laguna.

At least 19 recordsLinked to original sources
PubMed1994

Functional interaction between dopamine D1 and D2 receptors in 'MPTP' monkeys.

We have studied the motor response induced by independent administration of 4 different doses of a dopamine D2 [(+)-PHNO] and a dopamine D1 (CY 208-243) receptor agonist in 5 MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkeys. Both drugs had similar antiparkinsonian effects and both elicited choreic dyskinesias. Simultaneous administration of (+)-PHNO [(+)-4-propyl-9-hydroxynaphthoxazine] and CY 208-243 [(-)4,6,6a,7,8,12b-hexahydro-7-methylindolo[4,3a-b]phenan thyxidine] did not result in modification of the dose-response curve induced by each dopamine receptor agonist given alone. Pretreatment with the dopamine D1 receptor antagonist SCH 23390 (0.8 mg/kg) and the dopamine D2 receptor antagonist sulpiride (60 mg/kg) reduced the magnitude and the duration of the motor response induced by (+)-PHNO and CY 208-243, respectively, but did not modify the intensity and characteristics of choreic dyskinesias. These results demonstrate that the motor effects and the dyskinesias cannot be dissociated by selective dopamine D1 and D2 receptor stimulation. It appears that stimulation of dopamine D1 and D2 receptors by endogenous dopamine is required to obtain the full motor response induced by selective dopamine receptor agonists as demonstrated by the reduction of the motor improvement found after pretreatment with SCH 23390 and sulpiride.

Animals↗
PubMed1993

The AMPA receptor antagonist NBQX does not alter the motor response induced by selective dopamine agonists in MPTP-treated monkeys.

We studied the motor response induced by the administration of the AMPA receptor antagonist, NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo[f]quinoxaline(1H,4H)dione sodium salt), in two parkinsonian monkeys and its interaction with the selective D-2 dopamine receptor agonist, (+)-PHNO [(+)-4-propyl-9-hydroxynaphthoxazine], and the partial dopamine D-1 receptor agonist, CY 208-243 [(-)-4,6,6a,7,8,12b-hexahydro-7-methyl-indolo[4,3a-b]phen anthyxidine]. NBQX treatment did not reverse the parkinsonism or change the responses previously induced by dopamine agonists. These results do not support an antiparkinsonian effect of the AMPA receptor antagonist, NBQX. In addition they indicate that there is no functional interaction between AMPA and dopamine receptors in monkeys with a substantia nigra lesion.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

Behavioral tolerance to repeated apomorphine administration in parkinsonian monkeys.

Four consecutive injections (s.c.) of apomorphine (Apo) were given to 5 parkinsonian monkeys after i.v. MPTP administration. The minimal effective dose (MED) of Apo was defined as that capable of reducing motor disability by 50% or more for a minimum period of 30 min. Repeated apomorphine injections were given with an interval of 30 min after the motor effect of the previous injection had worn off or with a separation of 3 h between injections. The doses used in different experiments were the MED (2.4 micrograms/kg), 4 MED and 8 MED. In every experiment the duration of motor benefit was longest with the first Apo injection. There was a decay in the duration of the response elicited by consecutive Apo injections when given 30 min after the previous effect had waned. This was significant for the MED and 4 MED (ANOVA, P < 0.01). When Apo boluses were given with an interval of 3 h there was a significant reduction in the duration of the response elicited by the MED, 4 MED and 8 MED of apomorphine. For the MED the reduction in the duration of the motor response was significantly greater for injections given with a 30-min interval than 3-h interval. These findings indicate that behavioral hyposensitivity to repeated Apo administration in parkinsonian monkeys occurs preferentially when near threshold doses are given with short intervals.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

Does neuromelanin contribute to the vulnerability of catecholaminergic neurons in monkeys intoxicated with MPTP?

The question has been raised as to whether neuromelanin, a by-product of catecholamine metabolism which accumulates during aging in primate midbrain neurons, contributes to the selective vulnerability of subgroups of dopaminergic neurons in Parkinson's disease. 1-Methyl-4-phenylpyridinium (MPP+) a metabolite of 1-methyl, 4-phenyl, 1,2,3,6-tetrahydropyridine (MPTP) is toxic to dopaminergic neurons, particularly in primates, producing a motor syndrome similar to that observed in Parkinson's disease. To test whether this neurotoxin preferentially affects melanized neurons, the survival of melanized and non-melanized catecholaminergic neurons was analysed after MPTP intoxication in the midbrain of the cynomolgus monkey (Macaca fascicularis). Experiments were performed on six animals chronically treated with MPTP (two were severely disabled, four moderately affected) and two age-matched control monkeys. Two populations of neurons were examined on regularly spaced sections throughout the midbrain: catecholaminergic neurons, identified by tyrosine hydroxylase immunohistochemistry and neuromelanin-containing neurons, visualized by Masson's method. The total number of neurons of each type was estimated in the different midbrain catecholaminergic cell groups using computer assisted image analysis. In the midbrains of control animals not all catecholaminergic neurons contained neuromelanin. The percentage of melanized neurons compared to the total population of tyrosine hydroxylase-positive neurons was high in the substantia nigra pars compacta (81.5%) and in the locus coeruleus (98%), intermediate in the substantia nigra pars lateralis (70%), in the catecholaminergic cell group A8 (50%), and in the ventral tegmental area (41.5%) and almost nil in the central gray substance. In MPTP-treated monkeys, the severity of the loss of catecholaminergic neurons was variable within the different midbrain cell groups, though of similar intensity in severely and mildly disabled monkeys. A relationship was found between the loss of dopaminergic neurons in the different mesencephalic cell groups of MPTP-intoxicated animals and the percentage of melanized neurons they normally contain (r = 0.98; P = 0.04). The percentage loss of catecholaminergic neurons in the locus coeruleus, the only noradrenergic cell group studied, was lower than expected from the correlation curve obtained for dopaminergic cell groups. Altogether, these findings indicate: (i) that dopaminergic neurons are more vulnerable to MPTP-toxicity than noradrenergic neurons; and (ii) that among dopaminergic neurons, those containing neuromelanin are more susceptible, indicating a possible role of neuromelanin in MPTP-toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

[Risk factors for the heterosexual transmission of HIV from man to woman: a Spanish multicenter study].

BACKGROUND: The aims of this study were to estimate the rate of heterosexual transmission of HIV in a population of intravenous drug users (IVDU), as to well as to identify the possible risk factors associated. METHODS: One hundred thirty heterosexual couples were analyzed in which the male was seropositive for the human immunodeficiency virus (HIV) with the only possible risk factor for the companion being the sexual intercourse with the case index. RESULTS: The rate of global transmission estimated was 16% (confidence interval of 95% = 10-22.4%). The risk factors significantly associated to HIV transmission were: case index of over 30 years of age (OR = 3.1), clinical status IV (OR = 4.1), less than 0.8 x 10(8) lymphocytes/I (OR = 7), antecedents of sexually transmitted disease (STD) in the woman (OR = 4), and the practice of anal intercourse (OR = 3.1). In the multivariate analysis only the clinical status of the case index and the STC antecedents of the woman were statistically significant (p less than 0.05). CONCLUSIONS: In this study some of the classical risk factors for the heterosexual transmission of HIV have been confirmed, and the importance of decreasing the prevalence of STD in the IVDU collective in Spain has been corroborated to lower heterosexual transmission and, indirectly the vertical transmission of AIDS.

Chi-Square Distribution↗
PubMed1992

Selective D2 receptor stimulation induces dyskinesia in parkinsonian monkeys.

Stimulation of D1 striatal receptors has been proposed as the main mechanism mediating levodopa-induced dyskinesia in Parkinson's disease. We used (+)-PHNO, a selective D2 agonist, as the only treatment in 6 cynomolgus monkeys made parkinsonian by repeated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration. All animals developed choreic dyskinesia after a mean treatment period of 12.8 days (range, 1-29). Administration of the D1 antagonist SCH-23390 1 hour before administration of (+)-PHNO did not change the dyskinesia. These results indicate that drug-induced dyskinesia in a primate model of Parkinson's disease is not solely induced by D1 receptor activation.

Animals↗
PubMed1992

Motor response to repeated dopaminergic stimulation in Parkinson's disease.

Recent studies giving subcutaneous apomorphine or intravenous levodopa boluses have not found clear evidence of behavioral hyposensitivity to repeated dopaminergic stimulation in Parkinson's disease (PD). Here we analyze that data, and review experimental findings in animal models and our previous experience with parkinsonian patients. We conclude that acute tolerance to pulsatile stimulation is likely to play a role in the pathophysiology of motor fluctuations in PD.

Animals↗
PubMed1991

Controlled clinical trial of cannabidiol in Huntington's disease.

Based on encouraging preliminary findings, cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, was evaluated for symptomatic efficacy and safety in 15 neuroleptic-free patients with Huntington's Disease (HD). The effects of oral CBD (10 mg/kg/day for 6 weeks) and placebo (sesame oil for 6 weeks) were ascertained weekly under a double-blind, randomized cross-over design. A comparison of the effects of CBD and placebo on chorea severity and other therapeutic outcome variables, and on a Cannabis side effect inventory, clinical lab tests and other safety outcome variables, indicated no significant (p greater than 0.05) or clinically important differences. Correspondingly, plasma levels of CBD were assayed by GC/MS, and the weekly levels (mean range of 5.9 to 11.2 ng/ml) did not differ significantly over the 6 weeks of CBD administration. In summary, CBD, at an average daily dose of about 700 mg/day for 6 weeks, was neither symptomatically effective nor toxic, relative to placebo, in neuroleptic-free patients with HD.

Adolescent↗
PubMed1991

[Parkinsonism induced by MPTP as an experimental model of Parkinson disease: similarities and differences].

MPTP administration, preferably to mice and primates, induces a selective damage of substantia nigra dopaminergic cells. Intrinsic mechanisms mediating MPTP induced toxicity, remain still under evaluation. There are very few semiological differences between Parkinson's disease (PD) and MPTP parkinsonism, but significant biochemical and neuropathological differences have been reported between these two entities. However, at the moment it represents the best model of Parkinson's disease available for the study of the basal ganglia function. In addition it could be a useful tool for a better understanding of mechanisms involved in neuronal death and regeneration. The present paper, summarize the real knowledge about the mechanism by which MPTP induces neuronal toxicity, the differences reported between PD and MPTP parkinsonism and finally its application for research.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1990

Generalized reflex myoclonus in a patient with alcohol-sensitive spontaneous myoclonus and an abnormal gait.

A patient with alcohol-sensitive spontaneous, action- and stimulus-sensitive generalized reflex myoclonus is reported. Gait was abnormal but could not be clearly classified as dystonic. No other neurological abnormality was present. The possible relationship between alcohol-sensitive myoclonic dystonia and this case is discussed. Reflex myoclonus may serve as an additional clinical marker in the study of families with alcohol-sensitive myoclonus, dystonia, or both.

Adult↗
PubMed1990

Priming effects in a letter-by-letter reader depend upon access to the word form system.

Several types of cognitive and neuropsychological evidence suggest that priming effects on such implicit memory tests as word identification are mediated by a pre-semantic visual word form system that can operate independently of episodic memory. We investigate priming in a letter-by-letter reader, P.T., whose pattern of performance on neuropsychological tests indicates preservation of the word form system. Experiment 1 revealed robust priming on a word identification test following letter-by-letter study of target words, despite P.T.'s great difficulty in identifying non-studied words. Experiment 2 showed that the priming effect was modality specific whereas Experiment 3 indicated that recall of previously studied words was not modality specific, thus indicating that the observed priming could not be attributed to explicit memory strategies. Experiment 4 revealed no priming of illegal nonwords on a letter identification test. The results support the notion that priming on the word identification test depends on access to the word form system.

Attention↗