RESUMEN
Previous studies showed that chronic electroconvulsive shock (ECS) or imipramine treatment induced a subsensitivity of group I metabotropic glutamate receptors (mGluR) in hippocampus. In the present study effects of antidepressant treatment on the expression of mGluR1a and mGluR5a, belonging to the group I mGluR, were investigated in rat brain hippocampus using immunohistochemical and Western blot methods, respectively. Male Wistar rats were treated singly or chronically for 21 days with imipramine, 10 mg/kg, twice daily; with ECS (90 mA, 50 Hz, 0.5 s) every second day; or with haloperidol, 1.2 mg/kg, once daily. Appropriate controls were injected with saline. Rats were sacrificed 24 h after the last treatment and their hippocampi were taken out for analysis. It was found that the mGluR1a-immunoreactivity expression increased significantly in Ammon's horn (CA) regions after chronic ECS. The most pronounced effect was observed in the CA3. No significant effects were found after single treatment or after haloperidol. The expression of mGluR5a increased significantly after chronic imipramine in the CA1 and after chronic ECS in the CA3 region. The results obtained indicate an influence of antidepressant treatment on group I mGluR. This increase in the receptor protein level may be a compensatory mechanism developing after chronic treatment.
Asunto(s)
Electrochoque , Hipocampo/efectos de los fármacos , Imipramina/administración & dosificación , Receptores de Glutamato Metabotrópico/biosíntesis , Animales , Esquema de Medicación , Electrochoque/estadística & datos numéricos , Hipocampo/química , Hipocampo/metabolismo , Inmunohistoquímica , Masculino , Ratas , Ratas Wistar , Receptor del Glutamato Metabotropico 5 , Receptores de Glutamato Metabotrópico/análisisRESUMEN
Our earlier findings concerning the 6-OHDA lesion suggested dopaminergic regulation of neuropeptide Y (NPY) and corticotropin releasing factor (CRF) synthesis and expression in amygdala neurons. On the other hand, some other studies indicated that not only dopamine, but also other monoamines may modulate peptidergic neurons. Therefore the present study examined the effect of pharmacological deprivation of monoaminergic influences on NPY and CRF neurons in rat brain amygdala by means of in situ hybridization and immunohistochemical methods. It was found that NPY mRNA expression in the amygdala decreased after 24h blockade of dopaminergic D1 and D2 receptors, by haloperidol or SCH23390. At the same time the NPY-peptide expression measured immunohistochemically was not significantly changed. A prolonged, 14-day, blockade of dopaminergic receptors by haloperidol induced an opposite effect, an increase in NPY mRNA expression. Impairment of the serotonergic transmission by blockade of 5-HT synthesis using p-chlorophenylalanine, as well as attenuation of the noradrenergic transmission by NA depletion from terminals by DSP4, did not significantly change NPY mRNA expression or the mean number of NPY-immunoreactive neurons in the amygdala. Only a decrease in the staining intensity observed as a decreased number of darkly stained neurons was found after both compounds. Neither the dopamine receptor blockade nor the impairment of serotonergic or noradrenergic transmission changed CRF mRNA or the peptide expression in the amygdala. The obtained results indicate that in rat brain amygdala, of all the monoamines, dopamine seems to be the most important modulator of NPY biosynthesis and expression. The effect of blockade of dopaminergic receptors is biphasic: first it induces a decrease and then - after prolonged treatment an increase in NPY mRNA. Serotonergic and noradrenergic systems in the amygdala seem to be connected with regulation of NPY release rather than the biosynthesis.
Asunto(s)
Amígdala del Cerebelo/fisiología , Hormona Liberadora de Corticotropina/genética , Antagonistas de Dopamina/farmacología , Haloperidol/farmacología , Neuropéptido Y/genética , Amígdala del Cerebelo/química , Animales , Benzazepinas/farmacología , Hormona Liberadora de Corticotropina/análisis , Fenclonina/farmacología , Expresión Génica/efectos de los fármacos , Expresión Génica/fisiología , Inmunohistoquímica , Hibridación in Situ , Masculino , Neuropéptido Y/análisis , ARN Mensajero/análisis , Ratas , Ratas Wistar , Antagonistas de la Serotonina/farmacologíaRESUMEN
The effects of acute and chronic administration of 1,2,3,4-tetrahydroisoquinoline, an endogenous substance suspected of producing parkinsonism in humans, on the muscle tone and metabolism of dopamine in the striatum, and on the number of tyrosine hydroxylase-immunoreactive cells in the substantia nigra were investigated in rats. Muscle tone was examined using a combined mechanomyographic and electromyographic method which measured simultaneously the muscle resistance of the rat's hind foot to passive extension and flexion in the ankle joint and electromyographic activity of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior. 1,2,3,4-Tetrahydroisoquinoline administered at doses of 50 and 100 mg/kg intraperitoneally for 19 days increased muscle resistance 1 h after the first injection (acute treatment), 1 h after the last injection (chronic treatment) and three days after compound withdrawal. Rigidity observed on the third day of 1,2,3,4-tetrahydroisoquinoline withdrawal was accompanied by an increased tonic (resting) electromyographic activity of the gastrocnemius and tibialis anterior muscles. At the same time, a significant reduction in the number of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra and a decrease in the dopamine level in the striatum were also found. A declining number of tyrosine hydroxylase-immunoreactive neurons in the whole substantia nigra showed a significant negative correlation with the enhanced muscle resistance, as well as with the tonic electromyographic activity recorded at rest, i.e. before the start of movements, from the gastrocnemius and tibialis anterior muscles. Our results suggest that 1,2,3,4-tetrahydroisoquinoline may be one of the endogenous substances involved in the progress of Parkinson's disease.
Asunto(s)
Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Isoquinolinas/farmacología , Tono Muscular/efectos de los fármacos , Sustancia Negra/enzimología , Tetrahidroisoquinolinas , Tirosina 3-Monooxigenasa/metabolismo , Animales , Cuerpo Estriado/efectos de los fármacos , Electromiografía , Inmunohistoquímica , Masculino , Microdiálisis , Ratas , Ratas Wistar , Sustancia Negra/efectos de los fármacos , Factores de TiempoRESUMEN
The influence of dopaminergic denervation on neuropeptide Y and corticotropin-releasing factor-containing neurons in the amygdala was investigated in rats by examining the effects of a selective, unilateral 6-hydroxydopamine lesion of mesencephalic dopaminergic neurons in both the substantia nigra and the ventral tegmental area on these peptides and their messenger RNA expression, observed eight to 10 days after the lesion. The studies were conducted by immunocytochemical and in situ hybridization methods. Neuropeptide Y or corticotropin-releasing factor-immunoreactive neurons were counted in sections of the amygdala under a microscope, and the messenger RNA expression was measured as optical density units in autoradiograms. A significant increase in both neuropeptide Y and corticotropin-releasing factor messenger RNA expression was found in the amygdala on the lesioned side in comparison with the contralateral one, as well as with the ipsilateral side of vehicle-injected controls. Immunohistochemical studies showed that the number of neuropeptide Y-immunoreactive neurons increased in the whole amygdala on the lesioned side. At the same time, the number of corticotropin-releasing factor-immunoreactive neurons grouped in the central amygdaloid nucleus declined, and so did the staining intensity. The obtained results indicate that dopaminergic denervation stimulates the synthesis of neuropeptide Y and corticotropin-releasing factor in rat amygdala, but the peptide levels are differently regulated, which points to a diverse release of these peptides.
Asunto(s)
Amígdala del Cerebelo/metabolismo , Hormona Liberadora de Corticotropina/metabolismo , Neuropéptido Y/metabolismo , Oxidopamina/farmacología , Amígdala del Cerebelo/efectos de los fármacos , Animales , Hormona Liberadora de Corticotropina/genética , Histocitoquímica , Inmunohistoquímica , Hibridación in Situ , Masculino , Neuropéptido Y/genética , ARN Mensajero/metabolismo , Ratas , Ratas WistarRESUMEN
The effect of chronic imipramine (IMI) or electroconvulsive shock (ECS) treatment on the expression of group Ia metabotropic glutamate receptors (mGluR1a) was studied in the rat hippocampus by an immunohistochemical method, using a specific monoclonal antibody. It was found that both those treatments increased the number of mGluR1a immunoreactive neurons in a pyramidal layer of the CA3 hippocampal field. Moreover, IMI, but not ECS, increased the density of mGluR1 a positive neurons in the hilus. The obtained results indicate a possible influence of the antidepressive treatment on the mGluR1a expression in some hippocampal fields.
Asunto(s)
Antidepresivos/farmacología , Terapia Electroconvulsiva , Hipocampo/efectos de los fármacos , Células Piramidales/efectos de los fármacos , Receptores de Glutamato Metabotrópico/efectos de los fármacos , Animales , Antidepresivos Tricíclicos/farmacología , Hipocampo/metabolismo , Imipramina/farmacología , Inmunohistoquímica , Masculino , Células Piramidales/metabolismo , Ratas , Ratas Wistar , Receptores de Glutamato Metabotrópico/metabolismoRESUMEN
The effect of reserpine, a monoamine-depleting agent, on the neuropeptide Y (NPY) immunoreactivity was studied immunohistochemically in the amygdaloid complex (amygdala) of rat brain. It was found that reserpine, at a dose of 10 mg/kg i.p., after 24 h, enhanced the NPY immunoreactivity in amygdala neurons, which was expressed as an increase in the staining intensity and in the number of immunoreactive neurons visible in that structure. The obtained results suggest that monoamines take part in the regulation of NPY expression in amygdala neurons of rat brain, and that elimination of these monoaminergic regulation leads to an increase in the NPY content in that structure.
Asunto(s)
Amígdala del Cerebelo/química , Neuropéptido Y/análisis , Reserpina/farmacología , Animales , Inmunohistoquímica , Masculino , Neuronas/química , Neuropéptido Y/inmunología , Ratas , Ratas WistarRESUMEN
Neuropeptide Y (NPY), a 36-amino acid peptide, is present in some hippocampal interneurons and nerve terminals and seems to modulate glutamatergic transmission in this structure. Earlier studies of some other authors showed an increase in NPY expression in the hippocampus during seizures and activation of ionotropic glutamate receptors. In the present study the effect of metabotropic glutamate receptor (mGluR) stimulation was investigated in rat hippocampus by immunohistochemical methods. It was found that (1S,3R)1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), a selective agonist of mGluRs injected into the rat lateral ventricle (1 mumol/10 microliters) or hippocampus (0.1 mumol/1 microliter), 24 h before taking the brains for immunohistochemical studies, induced a significant increase in NPY-immunoreactivity in the hippocampus, especially in the hilar region. The obtained results indicate that mGluRs positively modulate the NPY content in the hippocampal neurons.