Biomedical subjects

M G Rosales

Publications and source records attributed to M G Rosales.

8 recordsLinked to original sources

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

Muscarinic antagonists microinjected into the subthalamic nucleus decrease muscular rigidity in reserpinized rats.

The ability of anticholinergic agents microinjected into the subthalamic nucleus to reduce reserpine-induced muscular rigidity was assessed in rats. The electromyographical activity of the gastrocnemius-soleus muscle was used as a parameter of muscular rigidity. Reserpine (5 mg/kg i.p.) produced the appearance of electromyographical activity. The muscarinic antagonists M3 (1.27 nmol of 4-DAMP) and M1 (2.36 nmol of pirenzepine) markedly reduced the reserpine-induced electromyographical activity, whereas the M2 antagonist AFDX-116 (2.37 nmol) had no effect. These results suggest that a high cholinergic tone in the subthalamic nucleus is associated with the reserpine-induced muscular rigidity. Moreover, the M3 muscarinic antagonist is more effective than the M1 muscarinic antagonist in reducing the muscular rigidity in reserpinized rats, a model of Parkinson's disease, by blocking the high cholinergic tone in the subthalamic nucleus.

Anesthetics, Intravenous↗

PubMed1996

M3 muscarinic receptors mediate cholinergic excitation of the spontaneous activity of subthalamic neurons in the rat.

The effect of the muscarinic antagonist on carbachol-induced increase in spontaneous activity of neurons of the subthalamic nucleus was examined by recording the extracellular unitary activity in an in vitro slice preparation. Carbachol produced (98% of the 263 neurons tested) an increase (twofold of the basal at 500 nM) of the discharge frequency. The EC50 for the carbachol-induced effect was 375 +/- 8.7 nM (mean +/- SEM). The response was blocked by muscarinic antagonists in a dose dependent manner. However, the IC50 (94 +/- 3 nM) for the M3 antagonist 4-diphenyl acetoxy-N-methyl piperidine methobromide (4-DAMP) was considerably less than the other muscarinic antagonists (M1 antagonist pirenzepine, IC50 1340 +/- 110 nM; M2 antagonist AF-DX-116, IC50 6780 +/- 690 nM). These results suggest that the cholinergic input to the rat subthalamic nucleus exerts a postsynaptic excitatory action and this effect is likely mediated via muscarinic receptor type 3.

Animals↗

PubMed1995

5-Hydroxytryptamine increases spontaneous activity of subthalamic neurons in the rat.

The effect of 5-hydroxytryptamine on the spontaneous activity of neurons of the subthalamic nucleus was examined by recording the extracellular unitary activity in an in vitro slice preparation. The most frequent response to 5-hydroxytryptamine (84% of 57 neurons tested) was an increase (twofold of basal at 10 microM) of the discharge frequency. The EC50 for the 5-hydroxytryptamine-induced effect was 1.8 +/- 0.5 microM (mean +/- SEM). The response was dose-dependently blocked by the serotoninergic antagonist mianserin and was not prevented by removal of calcium ions from the perfusing buffer. These results indicate that the serotoninergic input to the rat subthalamic nucleus exerts a postsynaptic excitatory action on most neurons of the nucleus.

Animals↗

PubMed1994

Activation of subthalamic neurons produces NMDA receptor-mediated dendritic dopamine release in substantia nigra pars reticulata: a microdialysis study in the rat.

Here we have studied whether the activation of the subthalamic neurons induces the release of dopamine (DA) from dopaminergic dendrites in the pars reticulata of the substantia nigra. Subthalamic neurons were activated by carbachol microinjected into the subthalamic nucleus. A microdialysis probe was implanted in the medial aspect of the pars reticulata to collect samples of the perfusate. Carbachol (1 microgram/0.25 microliter saline) enhanced (58 +/- 8% over basal values) nigral DA release. The enhancement was fully blocked by the NMDA antagonist AP5 added to the microdialysis medium perfusing the pars reticulata. Perfusion of the pars reticulata with NMDA also increased (125 +/- 25% over basal) nigral DA release. Again, AP5 reversed the effect. These results suggest that activation of the glutamatergic subthalamonigral pathway enhances dendritic DA release by activating NMDA receptors present on dopaminergic dendrites.

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↗

PubMed1993

Appearance of EMG activity and motor asymmetry after unilateral lesions of the dopaminergic innervation to the subthalamic nucleus in the rat.

The effects of unilateral injections of 6-hydroxydopamine into the subthalamic nucleus on muscular rigidity and on motor behavior were examined. Muscular rigidity was judged by the appearance of electromyographical activity in the gastrocnemius-soleus muscle and motor behavior by the turning induced by DL-methamphetamine. The unilateral injection of 6-hydroxydopamine produced the appearance of electromyographical activity ipsilateral to the injected side and ipsilateral turning in response to systemic administration of DL-methamphetamine. These results suggest that the dopaminergic innervation exerts a tonic inhibitory action on the spontaneous activity of the subthalamic neurons. The loss of this action would cause muscular rigidity and motor asymmetry.

Animals↗

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↗