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A Imperato

Publications and source records attributed to A Imperato.

At least 91 records · Page 5Linked to original sources
PubMed1987

The D-1 antagonist SCH 23390 stimulates while the D-1 agonist SKF 38393 fails to affect dopamine release in the dorsal caudate of freely moving rats.

SCH 23390, from doses of 0.012 mg/kg s.c., dose dependently stimulated the release of dopamine (DA) and the output of its metabolites, dihydroxyphenylacetic acid and homovanillic acid, in the dorsal caudate of freely moving rats implanted with transcerebral dialysis fibers. SKF 38393 failed to modify DA release and metabolism at doses of 5, 10 and 25 mg/kg s.c. but at 25 mg/kg s.c. it abolished the effect of 0.025 mg/kg of SCH 23390. Administration of gamma-butyrolactone (700 mg/kg s.c.), which blocks the firing of DA neurons, prevented the effect of 0.050 mg/kg s.c. SCH 23390. The results indicate that D-1 receptors control the release of DA, probably through stimulation of the firing of DA neurons.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1986

Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol.

The effect of the i.p. administration of ethanol on the release of dopamine (DA) and on the output of its main metabolites, dihydroxyphenylacetic acid and homovanillic acid, was estimated in the rat by transcerebral dialysis of two terminal dopaminergic areas, the nucleus accumbens and the dorsal caudate. Low doses of ethanol (0.25-0.5 g/kg i.p.) stimulated DA release specifically in the n. accumbens and elicited pure behavioral stimulation. Higher doses of ethanol (1.0-2.5 g/kg) elicited sedation and hypnosis and stimulated further DA release and dihydroxyphenylacetic acid and homovanillic acid output in the accumbens and, although less, also in the caudate. High doses of ethanol (5 g/kg i.p.) elicited long-lasting hypnosis and sedation and induced a depression followed by stimulation of DA release in the accumbens. DA release in the caudate was stimulated further. Low doses of apomorphine (0.05 mg/kg s.c.) reversed completely the stimulant effect of 0.5 g/kg of ethanol on behavior and on DA release in the accumbens. Moreover, the stimulation of behavior and of DA release in the accumbens elicited by 0.5 g/kg of ethanol were abolished completely by pretreatment with 700 mg/kg of gamma-butyrolactone, an agent which blocks DA firing and DA release. The results indicate that ethanol preferentially stimulates DA transmission in the mesolimbic system probably by activating the firing activity of mesolimbic DA neurons and provide direct evidence that these changes are involved in the motor stimulant effects of ethanol.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Dopamine release and metabolism in awake rats after systemic neuroleptics as studied by trans-striatal dialysis.

The method of trans-striatal dialysis has been applied here to the study of the release and metabolism of dopamine (DA) in the awake rat. DA and its acidic metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), present in the dialysates were separated by high performance liquid chromatography on reverse phase columns and estimated by electrochemical detection. In the awake rat, DA, DOPAC, and HVA could be recovered and quantitated in the dialysates for at least 4 days from the time of implantation of the dialysis tube. At a constant 2-microliters/min flow of Ringer in the dialysis tube, the output of the substances recovered in 20-min samples 24 hr after the implantation was as follows: DA, 0.318 +/- 0.035; DOPAC, 41.3 +/- 4.84; HVA, 32.98 +/- 3.79 (mean picomoles +/- SEM of six 40-microliters samples). The output of DA, DOPAC, and HVA decreased slowly so that 4 days after the implantation the output of DA was reduced by about 35% in respect to the 24-hr values. After a 24-hr recovery, drugs were administered and their effect on DA release and metabolism was investigated. Drugs of different chemical structure and spectrum, but having in common the property of blocking DA receptors and being effective neuroleptics such as haloperidol, sulpiride, and flupentixol, stimulated DA release and DOPAC and HVA output. Threshold doses for this effect were very low, being 0.012 mg/k, s.c., for haloperidol, 2.5 mg/kg, s.c., for (-)-sulpiride, and 0.025 mg/kg, s.c., for cis-flupentixol. This effect was stereospecific as the (+) form of sulpiride and the trans- form of flupentixol were at least 10 to 100 times less potent than their enantiomer. The stimulation of DA release was shorter-lasting than the stimulation of DA metabolism and sedation or catalepsy. Moreover, whereas DA release did not increase by more than 100% over basal values, DOPAC and HVA increased by more than 3 times after maximally effective doses of neuroleptics. gamma-Butyrolactone (200 mg/kg, i.p.) reversed haloperidol (0.1 mg/kg, s.c.), and sulpiride (20 mg/kg, s.c.) induced stimulation of DA release while it potentiated the stimulation of DOPAC and HVA output. These data indicate that stimulation of DA release by neuroleptics is strictly dependent upon stimulation of DA firing and that different mechanisms underline their effects on DA release and on DA metabolism.

4-Butyrolactone↗
PubMed1985

Rapid tolerance to neuroleptic-induced stimulation of dopamine release in freely moving rats.

The effect of repeated s.c. administration of various neuroleptics (haloperidol, sulpiride and cis-flupentixol) on the in vivo release and metabolism of dopamine (DA) was studied in freely moving rats using trans striatal dialysis coupled to reverse-phase high-pressure liquid chromatography with electrochemical detection. Acute administration of neuroleptics dose-dependently but transiently stimulates DA release whereas lastingly stimulating DA metabolism. Administration of a second dose of neuroleptic, 4 to 12 hr after a priming dose, fails to stimulate DA release or stimulates it less effectively than in normal rats. A normal stimulatory response of DA release is reinstated when at least a 24-hr delay between the two doses is allowed. In contrast, the ability of the second neuroleptic dose to affect DA metabolism is unchanged. The results indicate that rapid tolerance takes place to neuroleptic-induced stimulation of DA release but not of DA metabolism.

Animals↗
PubMed1984

Fastigial influences on postural tonus as studied by kainate lesions and by local infusion of GABAergic drugs in the rat.

Localized lesions with kainic acid (KA) and local infusion of GABAergic drugs were used to study the role of the nucleus fastigii (NF) in postural tonus. Unilateral axon-sparing KA lesions of NF resulted in ipsilateral limb extensor atonia and contralateral limb extensor hypertonus and abduction. This effect lasted for 3-8 days depending on the dose of KA. Lesions of sites adjacent to the NF failed to produce postural asymmetries. Local infusion of the GABA agonist muscimol (10-50 ng) in the NF produced a reversible postural asymmetry fenomenologically similar to that produced by KA lesions of NF. Infusion of agents blocking GABAergic transmission in the NF (bicuculline, picrotoxin) resulted in a postural asymmetry of inverted laterality in respect to that produced by muscimol. Bilateral KA lesions of NF or bilateral infusion of muscimol resulted in bilateral hyperextension-abduction of the limbs. Infusion of GABAergic drugs in areas adjacent to the NF failed to produce postural changes. The results are interpreted to indicate that the NF exerts a crossed inhibitory and a direct excitatory influence on limb postural tonus.

Animals↗
PubMed1984

Trans-striatal dialysis coupled to reverse phase high performance liquid chromatography with electrochemical detection: a new method for the study of the in vivo release of endogenous dopamine and metabolites.

A method for the estimation in rats of the in vivo release and metabolism of dopamine (DA) is described. The method is based on the dialysis principle and consists of inserting transversally in the striatum a thin (0.2 mm) dialysis tube (Amicon Vitafiber) which is then perfused with Ringer. The Ringer, flowing at a constant rate of 2 microliters/min in the dialysis tube, extracts low molecular weight substances from the surrounding tissue by way of simple diffusion along a concentration gradient. At the distal end of the dialysis tube, the Ringer is collected every 10 to 20 min and directly injected into a high performance liquid chromatographer (HPLC) equipped with reverse phase octadecyl sulfate columns which separate DA and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). These substances are then quantitatively estimated by oxidative electrochemical detection. The basal output of DA is 0.3 pmol/20 min, whereas the outputs of DOPAC and HVA are 60 and 20 pmol/20 min, respectively. In basal conditions the output of DA, DOPAC, and HVA is stable over at least 10 hr. Histological examination of the track left by the dialysis probe in rats after 10 hr of continuous dialysis reveals very little damage and normal neuronal morphology in the vicinity of the dialysis tube. Increase of the K+ concentration in the Ringer to 30 mM produced a sharp, reversible increase of DA output. Both the basal and K+-stimulated release were Ca++ dependent, because omission of Ca++ abolished basal and K+-stimulated DA release. Electrical stimulation of the nigrostriatal DA neurons in the medial forebrain bundle sharply increased DA output. Amphetamine sulfate in low doses (1.0 mg/kg, i.v.) produced a 9-fold increase in DA release and decreased DOPAC and HVA output. alpha-Methyl tyrosine (150 mg/kg, i.v.) reduced within 2 hr DA release to 15% of basal values and in parallel also decreased the output of DOPAC and HVA. Reserpine (5 mg/kg, i.p.) reduced DA release but in a slower fashion than alpha-methyl tyrosine and increased DOPAC and HVA. Pargyline (75 mg/kg, i.p.) produced a 4-fold increase of DA release, while it rapidly brought to zero DOPAC and HVA output. gamma-Butyrolactone (700 mg/kg, i.p.) rapidly and lastingly reduced DA, DOPAC, and HVA output. The biochemical and histological results obtained indicate that the method is suitable to estimate in the rat the changes in the release o f endogenous DA and its metabolites which take place in vivo under administration of centrally acting drug.

Animals↗
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

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

Behavioural effects of GABA-agonists and antagonists infused in the mesencephalic reticular formation - deep layers of superior colliculus.

Unilateral infusion of GABA-receptor antagonists (picrotoxin, bicuculline) in the mesencephalic reticular formation-deep layers of the superior colliculus (MRF-DLSC) elicits tight head-to-tail contralateral posturing but not active circling. Bilateral infusion of the GABA antagonists in the MRF-DLSC elicits compulsive gnawing and biting but not licking or sniffing. Infusion of GABA-receptor agonists (muscimol, THIP) in the MRF-DLSC while producing only minor or no motor or behavioural effects, drastically altered apomorphine effects; thus, unilateral infusion of muscimol resulted i tight, head-to-tail ipsiversive circling while bilateral infusion of muscimol converted the apomorphine-syndrome from stereotypy of high-intensity into pure compulsive forward locomotion devoid of sniffing. The results indicate that GABAergic mechanisms in the MRF-DLSC are of primary importance in the expression of motor and behavioural syndromes arising from the striatum.

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↗