Biomedical subjects

L Pani

Publications and source records attributed to L Pani.

48 records · Page 3Linked to original sources

PubMed1991

Flunarizine attenuates cocaine-induced inhibition of A9 dopaminergic neurons.

The intravenous administration of cocaine (0.5-8 mg/kg) produced a dose-related inhibition of the firing rate of substantia nigra (A9) dopaminergic (DA) neurons. Pretreatment with the calcium antagonist flunarizine (5 mg/kg i.v.) prevented cocaine-induced effects but failed to antagonize the inhibition of firing induced by a low dose of apomorphine (10 micrograms/kg i.v.). This finding rules out the possibility that flunarizine antagonism of cocaine effect might depend on DA autoreceptors blockade by flunarizine. It is suggested that flunarizine, by blocking calcium influx into DA neurons, prevents DA release from dendrites, thereby counteracting the main mechanism by which cocaine inhibits dopaminergic neuronal activity.

Animals↗

PubMed1990

Calcium receptor antagonists modify cocaine effects in the central nervous system differently.

The effect of different calcium antagonists on cocaine-induced dopamine (DA) release in the striatum, as measured by brain microdialysis in freely moving rats, and on cocaine-induced motor stimulation was studied. While two dihydropyridine calcium antagonists, nimodipine (20 mg/kg) and isradipine (2.5 mg/kg), prevented cocaine-induced DA release and motor stimulation, the diphenylalkylamine-type calcium antagonist flunarizine (20 mg/kg) strongly potentiated both effects of cocaine. Moreover, two calcium antagonists, verapamil (20 mg/kg) and diltiazem (20 mg/kg), were ineffective. The results indicate that various classes of calcium antagonists differ in their interaction with the effects of cocaine in the CNS and suggest that dihydropyridine calcium channel antagonists might be clinically useful for the treatment of cocaine abuse.

Amphetamine↗

PubMed1990

Flunarizine potentiates cocaine-induced dopamine release and motor stimulation in rats.

Pretreatment with flunarizine (20 mg/kg), a diphenylalkylamine calcium channel antagonist, markedly potentiated cocaine (10 mg/kg)-induced dopamine (DA) output from the ventral striatum, as measured by microdialysis in freely moving rats. Moreover, flunarizine enhanced cocaine-induced motor stimulation. Pretreatment with the D2 receptor antagonist (-)-sulpiride (25 mg/kg) potentiated cocaine-induced DA output but, unlike flunarizine, inhibited cocaine-induced motor stimulation. When added to striatal membrane preparations, flunarizine displaced [3H]spiperone binding with a Ki of about 100 nM. Since recent evidence indicates that the effects of cocaine are calcium-dependent and are prevented by dihydropyridine calcium antagonists, these findings suggest that the paradoxical potentiating effect of flunarizine is probably due to an interaction with the DA system and is not due to its calcium antagonist property.

Animals↗

PubMed1990

The non-competitive NMDA-receptor antagonist MK-801 prevents the massive release of glutamate and aspartate from rat striatum induced by 1-methyl-4-phenylpyridinium (MPP+).

The concentrations of dopamine (DA) and of the excitatory amino acids (EAAs) glutamate (Glu) and aspartate (Asp) were measured in dialysates from the striatum of awake rats in order to study the link between the release of DA and of EAAs induced by the infusion of 1-methyl-4-phenylpyridinium ion (MPP+). DA and EAAs were detected simultaneously by HPLC-EC. The infusion of MPP+ at the concentration of 1 mM elevated DA levels in the perfusates, but did not affect EAA release. However, MPP+ at 10 mM maximally stimulated Glu and Asp release to 230- and 68-fold of baseline, respectively. In this condition, pretreatment with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (5 mg/kg, i.p.) prevented the MPP(+)-induced EAA release. In contrast, MK-801 had no effect on DA release induced either by 1 or 10 mM MPP+. These results suggest that MPP(+)-induced DA and EAA release are independently regulated processes. In addition, the finding that MK-801 inhibits MPP(+)-induced EAA release suggests that EAAs may act on NMDA receptors to stimulate their own release through a positive-feedback mechanism.

1-Methyl-4-phenylpyridinium↗

PubMed1990

Brain dialysis and dopamine: does the extracellular concentration of dopamine reflect synaptic release?

We considered the drug-induced circling behaviour of rats monolaterally lesioned with kainic acid (KA) as a marker of the dopamine (DA) concentration in the synaptic space. D-Amphetamine produced a dose-related increase in the DA concentration of the dialysate from an intact striatum and a proportional number of ipsilateral circlings. Pargyline or L-dihydroxyphenylalanine (L-Dopa), alone or in combination with benserazide, increased the concentration of DA to a similar or even higher level than d-amphetamine, but failed to elicit a circling response. Apomorphine given after these drugs at the peak of DA accumulation always induced circling behaviour. The results suggest that released DA may undergo different inactivation processes before reaching the dialysis probe, and that these processes may be differentially affected by drug treatments. Alternatively, it may be suggested that DA can be released into the synaptic space, in a functional manner, or into the interstitial fluid, from where it cannot reach the synaptic receptors.

Animals↗

PubMed1990

Stress increases noradrenaline release in the rat frontal cortex: prevention by diazepam.

Foot-shock produced a more than 2-fold increase in noradrenaline (NA) release from the frontal cortex of freely moving rats. The effect of acute stress was almost completely prevented by the administration of diazepam (5 mg/kg i.p.). Diazepam alone inhibited cortical NA release, the maximal inhibition (-57%) being observed 90 min after the injection. Cortical NA release therefore appears to be a reliable index of central noradrenergic activity in response to stressful conditions.

Animals↗

PubMed1990