Biomedical subjects

J L Góngora-Alfaro

Publications and source records attributed to J L Góngora-Alfaro.

9 recordsLinked to original sources

PubMed2002

A novel rotometer based on a RISC microcontroller.

A new, low-cost rotometer, based on a reduced instruction set computer (RISC) microcontroller, is presented. Like earlier devices, it counts the number and direction of full turns for predetermined time periods during the evaluation of turning behavior induced by drug administration in rats. The present stand-alone system includes a nonvolatile memory for long-term data storage and a serial port for data transmission. It also contains a display for monitoring the experiments and has battery backup to avoid interruptions owing to power failures. A high correlation was found (r > .988, p < 2 x 10(-14)) between the counts of the rotometer and those of two trained observers. The system reflects quantitative differences in turning behavior owing to pharmacological manipulations. It provides the most common counting parameters and is inexpensive, flexible, highly reliable, and completely portable (weight including batteries, 159 g).

Animals↗

PubMed2001

Sleep and memory deficits in the rat produced by experimental infection with Trypanosoma cruzi.

We investigated whether the infection with Trypanosoma cruzi in rats could produce functional alterations of the central nervous system. The experimental group received an injection of 150,000 trypomastigotes / rat, whereas the control group received a saline injection. Spontaneous alternation behavior (SAB) tests and sleep-wake cycle recordings were obtained at the end of the parasitaemia. Results showed that the infected animals had significant sleep impairments, as denoted by an increase in the number of wake periods and a reduction of rapid eye movement sleep amount. SAB performance was also found to be impaired in these animals, as compared to the control group. Our results suggest that the rat is a suitable model for brain dysfunction studies in Chagas' disease.

Animals↗

PubMed1997

Firing frequency modulation of substantia nigra reticulata neurons by 5-hydroxytryptamine.

Unitary extracellular recordings were made in in vitro rat brain slices to explore the effects of serotoninergic analogues on the spontaneous activity of substantia nigra reticulata (SNr) neurons. Most SNr neurons exhibited regular spontaneous firing (23.4 +/- 8.9 Hz, mean +/- S.E.M., n = 30) similar to that found in vivo. The most reproducible effect of serotonin (5-HT) was an increase in firing frequency found in 53% of the cells. The effect was concentration dependent and blocked by the 5-HT1/2 antagonist methysergide (1-10 microM) but unaffected by the 5-HT4- and 5-HT1-preferring antagonists DAU 6285 (5 microM) and metiothepin (5 microM), respectively. However, 5-HT also decreased the firing frequency in several neurons. In 19% of the neurons an inhibition was found alone but a biphasic response (inhibition and excitation) was found in another 28% of the neurons. Interestingly, the effect of the 5-HT-uptake inhibitor, duloxetine (100-400 nM), was frequency inhibition. Agonists that mimicked the 5-HT-induced inhibition were of the 5-HT1B-class (25 microM CP 93129 and 25 microM TFMPP). Neither the 5-HT2-antagonist ritanserin (5 microM) nor the GABA(A)-antagonist, bicuculline (30 microM) were able to block the inhibition suggesting that some SNr neurons may be directly inhibited by 5-HT.

Animals↗

PubMed1997

Reciprocal interaction between glutamate and dopamine in the pars reticulata of the rat substantia nigra: a microdialysis study.

We studied the interactions between glutamate and dopamine in the pars reticulata of the substantia nigra by using microdialysis in unanaesthetized rats. Increased extracellular levels of glutamate in the pars reticulata were obtained by microinjecting the muscarinic agonist carbachol into the ipsilateral subthalamic nucleus. The increase of glutamate levels was followed by increments in extracellular levels of dopamine and GABA. Increased levels of the three neurotransmitters were also observed during the administration of N-methyl-D-aspartate through the microdialysis probe. The increase in glutamate and GABA caused by N-methyl-D-aspartate was blocked by SCH 23390, a selective D1 antagonist. However, the D1 antagonist did not prevent the increase in dopamine levels. The selective D1 agonist SKF 38393, added to the microdialysis probe, increased the levels of the three neurotransmitters. However, after the lesion of the subthalamic nucleus with kainic acid, SKF 38393 increased only the level of GABA but not those of glutamate and dopamine. In addition, the lesion of the subthalamic nucleus produced a drastic (80%) fall in the extracellular levels of glutamate. These data suggest that glutamate, through N-methyl-d-aspartate receptors, stimulates the release of dopamine from dopaminergic dendrites present in the substantia nigra pars reticulata, and that dopamine in turn stimulates the release of glutamate and GABA. Both effects are mediated by D1 dopamine receptors present on subthalamonigral and striatonigral axon terminals, respectively.

Animals↗

PubMed1996

Circling behavior elicited by cholinergic transmission in the substantia nigra pars compacta: involvement of nicotinic and muscarinic receptors.

The influence of cholinergic transmission within the substantia nigra pars compacta on circling behavior was assessed in male rats. Microinjection of physostigmine (6-37 nmol) into the caudal part of the substantia nigra pars compacta elicited a dose-dependent contralateral circling. The circling was inhibited 93 +/- 3% by the dopamine antagonist haloperidol (53 nmol) injected into the neostriatum 90 min before the injection of physostigmine (37 nmol) into the ipsilateral substantia nigra pars compacta. The effect of haloperidol was reversible, since the circling behavior was fully restored when physostigmine was applied to the same animals 24 h later. The circling was completely blocked when physostigmine (37 nmol) was applied simultaneously with the muscarinic M1 antagonist pirenzepine (2 nmol). The M2 antagonist AF-DX 116 (2 nmol) only partially blocked the circling induced by a lower dose of physostigmine (12 nmol). The nicotinic antagonist mecamylamine (5 nmol) also inhibited the circling, but only during the 5 min following co-injection of the drugs. These results indicate that endogenous acetylcholine stimulates muscarinic and nicotinic receptors of nigrostriatal dopaminergic neurons which, in turn, increase their firing rate and cause the circling behavior. We conclude that the pedunculopontine cholinergic neurons, which innervate the substantia nigra pars compacta, modulate the motor behavior by increasing the activity of dopaminergic nigrostriatal pathway.

Animals↗

PubMed1994

Cholinergic stimulation of rostral and caudal substantia nigra pars compacta produces opposite effects on circling behavior and striatal dopamine release measured by brain microdialysis.

Turning in circles is among the behaviors elicited by unilateral cholinergic stimulation of the substantia nigra. Recent studies have shown that microinjection of cholinergic agonists into the substantia nigra pars compacta increases dopamine release and turnover in the striatum of anesthetized rats [Hernández-López et al. (1992) Brain. Res. 598, 114-120; Blaha and Winn (1993) J. Neurosci, 13, 1035-1044]. In this study, the relationship between circling behavior and striatal dopamine release following cholinergic stimulation of the substantia nigra pars compacta neurons was assessed by brain microdialysis in awake rats. The results indicate that cholinergic stimulation of the substantia nigra pars compacta with the mixed nicotinic-muscarinic cholinergic agonist carbachol modulates striatal dopamine release, and this effect is accompanied by circling behavior and stereotypies. Microinjection of carbachol (109 nmol) in the caudal portions of the substantia nigra pars compacta induced contralateral circling associated with an increase of dopamine release in neostriatum. On the contrary, ipsilateral circling and reduction of striatal dopamine release was elicited when the same dose of the drug was applied in the rostral portions of the substantia nigra pars compacta. The above findings are in accordance with recent electrophysiological studies suggesting the existence of sub-populations of nigrostriatal dopaminergic neurons, and indicate that the substantia nigra pars compacta is functionally compartmentalized. We conclude that the cholinergic input to the substantia nigra pars compacta could modulate the motor behavior through regulating the firing rate of nigrostriatal dopaminergic neurons and dopamine release in the neostriatum.

Animals↗

PubMed1992

A cholinergic input to the substantia nigra pars compacta increases striatal dopamine metabolism measured by in vivo voltammetry.

3,4-Dihydroxyphenylacetic acid (DOPAC) and ascorbic acid (AA) were measured by differential pulse voltammetry in the neostriatum of anesthetized rats. Physostigmine (2.3 nmol) applied into the substantia nigra pars compacta (SNc), increased DOPAC concentration in the ipsilateral neostriatum, but did not modify AA levels. The largest increase of striatal DOPAC (37 +/- 8% above basal) was observed when physostigmine was applied at less than 0.5 mm from SNc, and decreased with increasing distance of the injection site from the pars compacta region. Chemical stimulation of the pedunculopontine tegmental nucleus (PPN) with kainic acid (2.3 nmol) increased both DOPAC and AA concentration in the ipsilateral neostriatum. Pretreatment with the muscarinic antagonist scopolamine (5 mg/kg, i.p.) inhibited the increase of striatal DOPAC from 20 to 70 min after kainic acid injection into the PPN, whereas the increase of AA was reduced from 90 to 160 min. By contrast, the nicotinic antagonist mecamylamine (4 mg/kg, i.p.) did not inhibit neither DOPAC nor AA increase elicited by the chemical stimulation of PPN. These results support the existence of cholinergic neurotransmission within the SNc that increases the firing rate of nigrostriatal dopaminergic neurons, enhancing dopamine turnover in neostriatum without changes in AA release. They also suggest that the PPN could be the origin of cholinergic afferents to the SNc that modulate the activity of dopaminergic neurons, through activation of muscarinic cholinergic receptors. Finally, the activation of a multisynaptic loop involving a cholinergic pathway which modulates the activity of the glutamatergic corticostriatal neurons is postulated to explain the increase of AA in neostriatum observed after PPN stimulation.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1992

NMDA receptor mediates dopamine release in the striatum of unanesthetized rats as measured by brain microdialysis.

We have studied the characteristics associated with the activation of the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor on the release of dopamine (DA) in the striatum of awake rats as measured by brain microdialysis technique. NMDA dose-dependently stimulated the striatal DA release in Mg(2+)-free Ringer's solution. The stimulation was significant at 90 microM and the maximum observed effect was at the highest concentration tested (800 microM). The selective NMDA receptor antagonist, 2-amino-5-phosphonovalerate (AP5; 300 microM), blocked the stimulatory effect of NMDA. The NMDA-induced release of DA was reduced by 1.2 mM Mg2+ and totally blocked by 2.5 mM of the cation. Glycine (200 microM) potentiated the response evoked by 300 microM NMDA while 7-chloro-kynurenate (100 microM), an antagonist of the glycine site, reduced markedly this response. Neither atropine (100 microM) nor tetrodotoxin (TTX) (5 microM) prevented the stimulatory effect of NMDA. These results suggest that glutamate released from corticostriatal terminals presynaptically stimulates the release of DA via an NMDA receptor.

2-Amino-5-phosphonovalerate↗

PubMed1991

Activation of nigral M1 and M2 muscarinic receptors produces opposing effects on striatal 3,4-dihydroxyphenylacetic acid measured by in vivo voltammetry.

3,4-dihydroxyphenylacetic acid (DOPAC) was measured by differential pulse voltammetry in the neostriatum of anesthetized rats. DL-Muscarine (2.9 nmol) applied into the substantia nigra pars compacta, increased DOPAC concentration in the ipsilateral neostriatum. This effect was blocked by pirenzepine (2.8 nmol), and potentiated by AF-DX 116 (2.8 nmol). These results indicate the existence of two types of muscarinic receptors on dopaminergic neurons, whose activation produces opposing effects on dopamine metabolism in neostriatum.

3,4-Dihydroxyphenylacetic Acid↗