PubMed Health⌕ Search

Biomedical subjects

M L Porceddu

Publications and source records attributed to M L Porceddu.

At least 37 records · Page 2Linked to original sources
PubMed1983

Role of ventral mesencephalic reticular formation and related noradrenergic and serotonergic bundles in turning behaviour as investigated by means of kainate, 6-hydroxydopamine and 5,7-dihydroxytryptamine lesions.

A unilateral kainate (KA) infusion (2 x 0.15 micrograms, 2 x 0.25 micrograms) in the ventral mesencephalic reticular formation (MRF) resulted in spontaneous contraversive turning lasting only a few days. Upon challenge with apomorphine (0.5 mg/kg s.c.) or amphetamine (5 mg/kg i.p.) the contraversive turning could be reinstated. The incidence, as well as the intensity, of the drug-induced response decreased over the 45 days of observation. KA infused in the ventral MRF induced typical lesions after doses of 2 x 0.15 micrograms but resulted in demyelination after 2 x 0.25 micrograms. These lesions failed to reduce noradrenaline (NA), serotonin (5 HT) or dopamine (DA) in various forebrain areas. Unilateral lesion of ascending NA projections by 6-OHDA infusion (4 micrograms) within the NA bundles coursing in the mesencephalon or near the locus coeruleus, failed to induce motor asymmetries. Unilateral selective lesion of the ventral NA bundle by local 6-OHDA (2 micrograms) infusion also failed to induce motor asymmetries, either spontaneously or in response to dopaminergic drugs. Unilateral lesion of ascending 5-HT projections by the tegmental infusion of 5,7-dihydroxytryptamine (10 micrograms) also failed to induce motor asymmetries in response to dopaminergic drugs but resulted in contraversive circling in response to 5-hydroxytryptophan. These data indicate that intrinsic neurones of the ventral MRF play a role in turning behaviour and exclude, in contrast with previous studies, a role of NA or 5-HT projections in the contraversive turning responses to DA receptor agonists obtained after lesions of the ventral MRF.

5,7-Dihydroxytryptamine↗
PubMed1982

Delayed inhibition of dopamine synthesis by gamma-butyrolactone and baclofen: dopamine autoreceptor supersensitivity?

The administration of gamma-butyrolactone (GBL) (750 mg . kg-1 i.p.) and baclofen (20 mg . kg-1 i.p.) to rats caused a transient increase followed by a long-lasting decrease in striatal dopamine (DA) synthesis, as measured by DOPA accumulation after decarboxylase inhibition. DA synthesis was reduced to 40-50% of the control value for 2-12 h following either treatment. The GBL- and baclofen-induced inhibition of DN synthesis was reversed by haloperidol (2-5 mg . kg-1 i.p.) and by a second dose of baclofen or GBL. The subcutaneous dose of 15 mg . kg-1 of apomorphine, insufficient to decrease DA synthesis in control rats, produced a further decrease in DA synthesis in animals pretreated with baclofen. These results suggest that the delayed DA synthesis inhibition following GBL or baclofen treatment was due to stimulation of supersensitive DA autoreceptors.

4-Butyrolactone↗
PubMed1982

A re-evaluation of the role of superior colliculus in turning behaviour.

There is much debate on the role of the superior colliculus (SC) in turning behaviour. In order to clarify this issue, unilateral kainate lesions were made by infusing 0.25 microgram of kainate at two different anterior planes (0.8 mm apart), in the lateral or in the medial aspects of the deep collicular layers (DLSC), in the dorsal mesencephalic reticular formation (MRF), or in the lateral periaqueductal grey (PAG), both in normal rats and in rats made unilaterally supersensitive to DA-receptor agonists by unilateral infusion of 6-OHDA in the rostral substantia nigra. The effect of kainate lesions on spontaneous and apomorphine-induced motor behaviour was studied. In normal rats, unilateral kainate lesions of lateral DLSC or dorsal MRF resulted in short-lasting, spontaneous ipsiversive turning and persistent ipsiversive circling after peripheral administration of apomorphine. In 6-OHDA rats, kainate lesions of lateral DLSC or of dorsal MRF ipsilateral to 6-OHDA denervation reduced or even reversed the contralateral circling normally elicited in these rats by peripheral administration of apomorphine. Lesions of dorsal MRF, when compared with lesions of lateral DLSC, were more effective in producing these changes. Kainate lesions restricted to medial DLSC or to the PAG failed to elicit motor asymmetries in normal rats or to significantly modify the intensity of contralateral turning in 6-OHDA rats. These results clearly indicate that the SC plays an important role in turning behaviour. Failure of previous studies to research this conclusion probably derives from inadequate localization of collicular lesions and from the use of bilateral lesions.

Animals↗
PubMed1981

Role of substantia nigra pars reticulata neurons in the expression of neuroleptic-induced catalepsy.

Bilateral kainate-induced lesions of the substantia nigra prevented or dramatically reduced the catalepsy produced by haloperidol. In contrast, infusion of 1 or 4 micrograms 6-OHDA in the medial forebrain bundle, which decreased striatal DA by 30% and 80% respectively, failed to affect or actually potentiated haloperidol catalepsy. Since intranigral kainate, in contrast to 6-OHDA, destroys pars reticulata neurons it appears that these neurons are essential for the expression of haloperidol-catalepsy.

Animals↗
PubMed1981

Role of dorsal mesencephalic reticular formation and deep layers of superior colliculus as out-put stations for turning behaviour elicited from the substantia nigra pars reticulata.

In order to investigate the role of dorsal mesencephalic reticular formation (MRF) and deep layers of superior colliculus (DLSC) as out-put areas for non-dopamine mediated behavioural functions arising in the substantia nigra, discrete unilateral kainate-lesions as well as sham-lesions were placed in the MRF and DLSC. Ten days later kainate (0.75 microgram) was microinjected into the substantia nigra pars reticulata. Lesions of MRF as well as lesions of DLSC reduced the contralateral turning induced by kainate lesions of pars reticulata ipsilateral to the MRF or DLSC lesions. The lesions of MRF were more effective than lesions of DLSC. Lesions of MRF or DLSC on the side contralateral to intranigral kainate were ineffective. The results indicate that the MRF-DLSC complex is an essential area for the expression of motor behaviour elicited from the substantia nigra.

Animals↗
PubMed1981

Role of dorsal mesencephalic reticular formation and deep layers of superior colliculus in turning behaviour elicited from the striatum.

Kainate or electrolytic lesions were placed unilaterally in the dorsal mesencephalic reticular formation (MRF) or in the deep layers of the superior colliculus (DLSC) on the same side of a unilateral lesion of the medial forebrain bundle with 6-OHDA. Before the lesions the rats turned contralaterally when challenged with 0.25 mg/kg of apomorphine. After lesions of the MRF most rats turned ipsilaterally in response to the same dose of apomorphine. After lesions of the DLSC apomorphine-induced contralateral turning was significantly reduced but not abolished. The results indicate that the MRF and DLSC play a primary role in the expression of turning originated from the striatum.

Animals↗
PubMed1981

Benzodiazepines prevent kainate-induced loss of GABAergic and cholinergic neurons in the chick retina.

Kainic acid (50 nmol), applied intravitreally to the eyes of chicks, produces within 6 h a loss of more than 50% of biochemical markers for cholinergic and GABAergic neurons in the retina. Repeated peripheral administration of benzodiazepines, such as diazepam and clonazepam, protects from the kainate-induced loss of cholinergic and GABAergic markers in the retina. Histologically diazepam reduces the nuclear pyknosis induced by kainate particularly at the level of the amacrine cell-layer.

Animals↗
PubMed1980

Lesions of substantia nigra by kainic acid: effects on apomorphine-induced stereotyped behaviour.

Fifteen days after bilateral lesions of the substantia nigra by local infusion of kainic acid (0.75 microgram) or after intranigral injection of vehicle, rats were administered 0.1, 0.25, 1.0 and 2.5 mg/kg s.c. of apomorphine and the stereotyped items (locomotion, sniffing and gnawing) were recorded on an event-recorder and motility was measured by a photocell apparatus. After low doses of apomorphine (0.1, 0.2 mg/kg), rats lesioned in the substantia nigra with kainic acid showed a degree of stimulation of motility and of sniffing similar to controls; on the other hand, in rats lesioned with kainic acid in the nigra, a dramatic reduction of gnawing and its replacement by sniffing was observed after administration of higher doses of apomorphine (1.0, 2.5 mg/kg). Bilateral infusion of kainic acid (0.75 microgram) into the reticular information, 2.0 mm dorsal to the substantia nigra, had no effect on apomorphine-induced stereotyped behaviour. These results are in agreement with the concept that the substantia nigra, through non-DA pars reticulata neurons, mediates motor and behavioural syndromes of striatal origin.

Animals↗
PubMed1980

Effect of discrete kainic acid-induced lesions of corpus caudatus and globus pallidus on glutamic acid decarboxylase of rat substantia nigra.

Locally applied kainic acid was used in order to destroy pallidal perikarya without damaging axons en passage, in an effort to clarify the role of the globus pallidus as a source of nigral GABAergic terminals. Rats were microinjected unilaterally with kainic acid in the globus pallidus, head, body and tail of the caudate and were sacrificed 7 days later. The forebrain of each rat was examined histologically in order to establish the extent of the lesion and nigral glutamate decarboxylase (GAD) was assayed as a marker of GABAergic terminals. Kainic acid produced in the globus pallidus loss of neuronal perikarya and reactive gliosis. Large multipolar neurons of the globus pallidus were characteristically absent on the lesioned-side. Lesions of the pallidum resulted in a non-significant (5.5%) reduction of nigral GAD. Kainate lesions restricted to the head of the caudate resulted in a significant (19%) drop of nigral GAD, while lesions of the caudate body provided the largest reductions of nigral GAD (53%). Lesions of the caudate tail were without effect. The results indicate that nigral GAD arises mostly from the body and, in part, also from the head of the caudate but not from the globus pallidus or from the tail of the caudate.

Animals↗
PubMed1980

Loss of striatal neurons after local microinjection of colchicine.

Intrastriatal injections of colchicine (4 micrograms) produced irreversible striatal damage characterized 30 days later by loss of intrinsic striatal neurons, gliosis and shrinkage but no apparent damage to myelinated bundles of the internal capsule. This neuronal loss was associated with a dramatic reduction of striatal and nigral glutamate-decarboxylase (GAD), the marker of GABA-ergic synapses and of striatal choline-acetyltransferase (CAT), the marker of cholinergic synapses. The levels of dopamine (DA) and serotonin (5HT) in the striatum as well as those of their metabolites were also reduced, indicating that colchicine exerts toxic effects also on terminals of striatal afferent neurons.

Animals↗
PubMed1979

Evidence for a GABAergic projection from the substantia nigra to the ventromedial thalamus and to the superior colliculus of the rat.

Unilateral intranigral infusion of kainic acid (1.5 microgram) produced neuronal loss in the lateral two-thirds of the nigra while sparing axons en passage. Fink-Heimer silver impregnation revealed dense terminal degeneration in the nigra itself (both in the compacta and in the reticulata) and in areas of non-dopaminergic nigral projection such as the ventromedial (VM) nucleus of the thalamus, the superior colliculus and the reticular formation; only spare terminal degeneration was found in areas of dopaminergic projection such as the caudate and septum. In order to clarify the nature of the transmitter of the nigrothalamic and nigrocollicular neurons, the activity of glutamic decarboxylase (GAD), the marker of cholinergic neurons, was measured in the VM and ventrobasal (VB) thalamus and in the nigra of each side, 7 days after unilateral intranigral injection of kainic acid. GAD activity was reduced significantly in the VM-thalamus (-33%), in the superior colliculus (-40%) and in the substantia nigra (-18%) but not in the VB-thalamus of the lesioned side. CAT remained unchanged in these areas. Similar results were obtained in the thalamus and in the superior colliculus after electrocoagulative lesions of the nigra. The results indicate the existence of a nigrothalamic and of a nigrocollicular GABAergic pathway. This projection might play an important role in motor coordination and gaze control.

Animals↗
PubMed1979

Substantia nigra as an out-put station for striatal dopaminergic responses: role of a GABA-mediated inhibition of pars reticulata neurons.

Intranigral administration of kainic acid results in loss of pars reticulata neurons without damage to axons traversing or terminating within the nigra. Unilateral nigral lesions with kainic acid result in an ipsilateral turning upon administration of apomorphine, a dopamine (DA)-receptor agonist and in contralateral turning upon administration of haloperidol, a DA-receptor blocker. Destruction of post-synaptic structures in the striatum of the side contralateral to that injected with kainic acid results in a drastic reduction, abolition or even reversal of the turning effects elicited by apomorphine and haloperidol. Unilateral intranigral microinjection of nanogram amounts of the GABA-receptor antagonists picrotoxin and bicuculline elicits ipsilateral circling upon apomorphine administration. Kainic-induced lesion or microinjection of picrotoxin or bicuculline in the nigra ipsilateral to a 6-OHDA-lesion of nigro-striatal DA-neurons results in reduction, abolition or reversal of the contralateral circling produced by apomorphine. The results indicate that the nigra pars reticulata is a station for dopaminergic impulses originating from the striatum and suggest that the turning behavior in response to striatal DA-receptor stimulation is due to a GABA-mediated inhibition of ipsiversive pars reticulata neurons.

Animals↗
PubMed1979

Opposite turning effects of dainic and ibotenic acid injected in the rat substantia nigra.

Unilateral intranigral administration of kainic and ibotenic acid, two putative stimulants of glutamatergic mechanisms, elicited turning behaviour starting from doses of 10 ng. While the turning produced by kainic acid was ipsilateral, that produced by ibotenic acid was contralateral to the injected side. Previous destruction of dopaminergic neurons on the side of the intranigral injection failed to reduce the turning behaviour. Peripheral treatment with picrotoxin did not reduce the turning in response to ibotenic acid. The results might suggest the existence of excitatory and inhibitory glutamate receptors which control nigral non-dopaminergic neurons mediating turning-behaviour.

Animals↗