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The administration of subconvulsive doses of kainic acid (5 mg/kg, intraperitoneally) to rats, with lesion of the substantia nigra pars reticulata (1 week), produced high frequency wet dog shakes and severe convulsive behavior (observed in 60% of the rats). The behavior was not observed in rats treated with kainic acid but without reticulata lesion. The results show that rats with unilateral lesion of the substantia nigra pars reticulata are more vulnerable to seizure stimuli.

The substantia nigra pars reticulata (SNpr) has been proposed to play an important role in the control of the propagation and/or the generation of epileptic seizures. Earlier studies have shown differential effects of the lesion of the SNpr on seizure genesis that demonstrated a regional difference in the anterior and posterior parts of the SNpr in preconvulsive behavior induced by unilateral reticulata injection of dopamine (DA). This study was aimed to investigate some of the underlying mechanisms of the preconvulsive behavior elicited by unilateral SNpr DA injection by the study of changes in the gene expression of glutamate receptor subunits (GluR1, GluR2 and NMDAR1) and of changes in animal behavior following coinfusion of DA and a DA D1 antagonist SCH 23390 into the SNpr. Unilateral injection of exogenous DA into the anterior region of the SNpr induced rapid and short lasting preconvulsive behavior up to wet dog shakes stage and a significant reduction of gene expression for GluR1, GluR2 and NMDAR1 subunits in rat hippocampal subfields including CA1 through CA4 and dentate gyrus (DG) at 1 day after nigral DA injection. The effect was long lasting and persisted for at least 3 weeks. Both preconvulsive behavior and downregulation of glutamate receptor subunit genes were completely blocked by simultaneous coinfusion of DA and SCH 23390. The results suggest, for the first time, that DA D1 receptor in the SNpr may mediate the nigral-involved seizure development. Glutamate desensitization, and/or selective early neuronal damage might be responsible for the downregulation of glutamate receptor subunits by transient preconvulsive activity.

This is a study of the effect of the unilateral administration of dopamine (DA) in the pars compacta of the substantia nigra (SN) of the rat on striatal glutamate receptor subunit (GluR1, GluR2 and NMDAR1) gene expression determined by in situ hybridization. The location of the nigral lesion was determined by tyrosine hydroxylase (TH) immunohistochemistry and its extent by the striatal DA and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations. The DA-induced lesions produce significant bilateral reductions in the expression of GluR1 and NMDAR1 subunit mRNA in the medio-lateral striatum, whereas the expression of striatal GluR2 receptors was not changed. The reduction in GluR1 and NMDAR1 subunit mRNA may be the consequence of glutamatergic hyperactivity developed in the presence of a damaged nigro-striatal system and these may be associated with the genesis of some neurodegenerative diseases.

The substantia nigra pars reticulata (SNpr) has been proposed to play an important role in controlling the propagation and/or the generation of limbic seizures. Earlier work has shown that SN lesions have differential effects on seizure activity, suggesting that at least two discrete topographical regions mediate anticonvulsant or proconvulsant effects. The present investigation showed that exogenous dopamine (DA; 1.5-2.0 mumol) unilaterally injected into the anterior SNpr induced preconvulsive behavior (starting, immobilization, facial and mouth movements and wet-dog shakes). In addition, these rats showed Fos oncoprotein expression in the limbic system. These effects were observed in 90% of the rats with anterior SNpr DA injection. Rats with posterior SNpr injection did not show preconvulsive behavior nor Fos expression. These results show for the first time that unilateral DA lesion of the anterior portion of SNpr elicits Fos expression and preconvulsive behavior. In addition, the results suggest that lesion of the anterior and posterior regions of SNpr appear to exert different influences in the generation of preconvulsive behavior. The time course of behavior changes and Fos expression was also studied.

Cultured astrocytes contain immunologically specific aromatic L-amino acid decarboxylase (AADC) protein and express the AADC gene. Following incubation with L-Dopa, glial cultures synthesize and metabolize dopamine. The addition of pyridoxal 5-phosphate did not change the rate of dopamine synthesis. The formation of dopamine was blocked by NSD-1015. These experiments show that mouse cultured astrocytes are capable to convert L-Dopa into dopamine in a dose-dependent fashion.

The addition of L-3,4-dihydroxyphenylalanine, L-5-hydroxytryptophan or m-tyrosine to cultured isolated astrocytes does not elicit the synthesis of either dopamine, 5-hydroxytryptamine or m-tyramine, respectively. In contrast, the astrocytes show ability to take up and store dopamine and 5-hydroxytryptamine that are in turn respectively metabolized to 3,4-dihydroxyphenylacetic acid or 5-hydroxyindoleacetic acid. These findings suggest that astroglial cell cultures lack aromatic-L-amino acid decarboxylase and give further evidence that these cells contain monoamine oxidase.

This report shows the existence of endogenous p-tyramine in the nerve cord and some organs of the lobster. Their concentrations are lower than those of dopamine or 5-hydroxytryptamine. The nerve cord levels of m-tyramine, beta-phenylethylamine and tryptamine are much lower than those of the phenolic or catecholic amines. The finding that the administration of an aromatic-L-amino acid decarboxylase inhibitor leads to a decrease of p-tyramine gives further evidence that this amine is synthesized from p-tyrosine, which is also found in high concentrations in the lobster nerve cord. The widespread distribution of p-tyramine in the nervous system and peripheral tissues of the lobster suggests that this amine may have additional roles rather than functioning only as a precursor of p-octopamine.

[3H]Tryptamine binding characteristics and responsiveness of spontaneously active caudate nucleus neurons to intravenous application of drugs were assessed 6 weeks following unilateral application of 6-hydroxydopamine (6-OHDA, 8 micrograms) to the substantia nigra of male Wistar rats. The effects of this lesion procedure on caudatal levels of dopamine, 5-hydroxytryptamine (5-HT) and their acid metabolites, and on pargyline-induced (200 mg/kg, 2 h, s.c.) accumulation of tryptamine in the caudate nucleus were also assessed. Levels of caudatal dopamine and metabolites were reduced ipsilateral to the lesion. Concurrently there was a reduction in the extent of pargyline-induced tryptamine accumulation. Caudatal [3H]tryptamine binding was increased ipsilateral to the lesion, indicating a postsynaptic localization of this binding site. Bmax values in the caudatal samples ipsilateral to the lesion were increased by an average of 34% relative to the contralateral side. Contralateral Bmax values were equivalent to those routinely obtained in control animals. The affinity (Kd) of these binding sites for [3H]tryptamine was unchanged by the lesion procedure. The firing rate of caudate neurons was inhibited by intravenous application of tryptamine, apomorphine and 5-MeODMT. The lesion procedure did not affect these responses to 5-MeODMT. Responses to tryptamine and to apomorphine were enhanced ipsilateral to the lesion by 10- and 3-fold respectively. Haloperidol (0.5 mg/kg, i.v.) reversed apomorphine-induced inhibition of caudatal neuronal firing rate. The effects of tryptamine were not reversed by haloperidol. These data indicate a classical adaptive increase in [3H]tryptamine binding in caudate following 6-OHDA lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

The concentrations of p-tyramine and m-tyramine have been determined in 6 brain areas from the mesolimbic system by a specific and sensitive mass spectrometric technique. p- and m-Tyramine are unevenly distributed amongst these nuclei. The highest concentrations of p-tyramine were measured in the olfactory tubercle followed by the nucleus accumbens and septal nuclei while for m-tyramine the concentrations decreased in the following order: olfactory tubercle, nucleus accumbens, amygdala, septal nuclei and nucleus tractus diagonalis.

Tryptamine is an indolic compound that occurs naturally in the mammalian central nervous system. To test whether tryptamine-containing neurons are present in the nigrostriatal system, we investigated effects of unilateral electrolytic lesions of the substantia nigra on striatal tryptamine concentrations. Determinations were made 7 days after lesioning. Nigral lesions resulted in an ipsilateral reduction in accumulation of striatal tryptamine observed after monoamine oxidase inhibition. As tryptamine formation is dependent on the activity of the enzyme L-aromatic acid decarboxylase (L-AAD), which is present in monoamine-containing neurons, the reduction in accumulation of tryptamine after nigral lesions may be secondary to enzyme loss with the degeneration of dopamine-containing neurons. Nevertheless, failure to observe decreases in the accumulation of tryptamine after raphé lesions, which deplete striatal 5-HT and L-AAD, indicates that tryptamine may be associated specifically with neurons in the nigrostriatal system.