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M Diana

Publications and source records attributed to M Diana.

16 recordsLinked to original sources
PubMed1992

Marked decrease of A10 dopamine neuronal firing during ethanol withdrawal syndrome in rats.

The electrophysiological activity of mesoaccumbens dopaminergic neurons was monitored during the ethanol-withdrawal syndrome in ethanol-dependent and in control rats. Spontaneous firing was reduced by about half in ethanol-dependent rats as compared to controls. Likewise, the number of spikes/burst was also reduced in ethanol-dependent rats. These results are consistent with the reduction in dopamine release observed during ethanol-withdrawal syndrome and may provide the basis for the aversive effects of the ethanol-withdrawal syndrome.

Animals↗
PubMed1992

Haloperidol-induced vacuous chewing in rats: suppression by alpha-methyl-tyrosine.

Chronic treatment of rats with haloperidol (1 mg/kg twice daily for 4 weeks) induced repetitive vacuous chewing movements (VC), that persisted for over 72 h after haloperidol withdrawal. Haloperidol-induced VC were inhibited by the s.c. administration of the specific dopamine D1, receptor antagonist, SCH 23390 (0.025-0.100 mg/kg), in a dose-dependent manner, and were totally suppressed by an acute challenge with haloperidol (2 mg/kg i.p.) and by the dopamine synthesis inhibitor, alpha-methyl-tyrosine (AMT) (200 mg/kg i.p.). In AMT-treated rats, VC were reinstated by the administration of the selective D1 agonist, SKF 38393. The results support the hypothesis that chronic haloperidol-induced VC are mediated by dopamine acting selectively upon D1 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Alcohol withdrawal in rats is associated with a marked fall in extraneuronal dopamine.

Withdrawal of rats from chronic ethanol (2-5 g/kg, every 6 hr for 6 days) resulted in withdrawal symptomatology and dramatic fall in extracellular dopamine (DA) in the ventral striatum as measured by microdialysis. The changes in DA output paralleled the withdrawal symptomatology and both phenomena were reversed by a challenge ethanol dose (5 g/kg orally). The results suggest that the decrease in DA output may be responsible for the aversive symptoms of withdrawal.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Lack of tolerance to ethanol-induced stimulation of mesolimbic dopamine system.

Rats maintained for 10 days on a 10% ethanol solution as the sole source of fluid developed marked tolerance to ethanol-induced loss of righting reflex, but no tolerance to the stimulatory effects on mesolimbic dopaminergic system. An ethanol challenge stimulated both the electrical activity of A10 dopaminergic cells and dopamine output in the ventral striatum of behaviourally tolerant animals and of controls to the same extent. These results are compatible with the hypothesis that an increased dopamine neurotransmission in the limbic system participates in the reinforcing effect of ethanol.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Low doses of gamma-hydroxybutyric acid stimulate the firing rate of dopaminergic neurons in unanesthetized rats.

In unanesthetized rats the intravenous (i.v.) administration of gamma-hydroxybutyric acid (GHB) at the doses of 50-400 mg/kg produced a dose-related stimulation (10-56%) of the firing rate of dopaminergic (DA) neurons in the pars compacta of the substantia nigra. Doses of 1000 and 1500 mg/kg inhibited the firing rate almost completely. In unanesthetized rats the intraperitoneal injection of GHB at the dose of 750 mg/kg produced a brief initial stimulation (23%) followed by a modest reduction in the firing rate (29%). On the other hand, in chloral hydrate-anesthetized rats the i.v. administration of GHB at cumulative doses of up to 200 mg/kg failed to modify the firing rate of DA neurons, while a cumulative dose of 400 mg/kg suppressed neuronal firing. The results indicate that sub-anesthetic doses of GHB stimulate the firing rate of DA neurons in unanesthetized rats.

Anesthesia, General↗
PubMed1991

Modulation of dopaminergic terminal excitability by D1 selective agents: further characterization.

We have previously shown that stimulation of striatal D1 receptors affects dopaminergic nigrostriatal terminal excitability, which is thought to be an index of biophysical events resulting from the activation of receptors on the presynaptic membrane. The experiments presented here further examine the locus and bases of these D1 effects in the rat. We now report that striatal administration of the D1 receptor selective antagonist R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazapine+ ++-7-ol-HCl (SCH 23390) produces a paradoxical agonist-like decrease in dopaminergic terminal excitability. This effect is blocked by pretreatment with the dopamine synthesis inhibitor, alpha-methyl-paratyrosine, suggesting that the action of SCH 23390 is dependent upon endogenous dopamine. Further, haloperidol pretreatment also prevents the SCH 23390-induced decrease in terminal excitability, confirming that dopamine, acting through a dopamine receptor, is responsible for this agonist-like action. Striatal application of the active R-(+) enantiomer of the dopaminergic D1-selective agonist 1-phenyl-2,3,4,5-tetrahydrol-(1H)-3-benzazepine-7,8-diol-HCl (R-SKF 38393) decreases terminal excitability in the alpha-methyl-paratyrosine pretreated animal, indicating that dopamine is not required for the agonist action. In an effort to ascertain the presynaptic or postsynaptic location of these actions, an extensive destruction of postsynaptic neurons in the neostriatum was produced by local administration of the neurotoxin, kainic acid. It was observed that the neurotoxin-induced neostriatal neuronal loss did not disrupt the action of R-SKF 38393 nor its reversal by SCH 23390.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
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↗
PubMed1989

Electrophysiological analysis of dopamine cells from the substantia nigra pars compacta of circling rats.

Extracellular single unit recordings were obtained from dopamine cells in the substantia nigra pars compacta during forced locomotion on a circular turntable treadmill. Stainless steel wire electrodes, 18 microns diameter, insulated with Parylene C were used. During the entire recording session the rat was in the treadmill apparatus. The device was stopped while a cell was being sought. A cell was identified as dopaminergic by a frequency of 3 to 10 Hz and a biphasic or triphasic action potential of greater than 2 ms in duration. An attempt was made to record from cells under the following conditions: animal at rest, animal turning in one direction, at rest again, turning in the opposite direction and finally, at rest. If the cell was still firing after these recordings, haloperidol was injected i.p. to see that the presumed dopamine cell increased its firing rate. A cell was held for all the observations in 4 animals. In an additional 10 rats, recordings were made before, during and after movement in one direction. Three animals were recorded only before and during movement. In 6 of the total of 17 animals haloperidol was administered. Results showed that firing patterns of cells in awake animals were similar to those reported from dopamine cells of anesthetized rats. During either contralateral or ipsilateral turning the firing frequency and burst activity significantly increased. These results indicate that the activity of dopamine cells in substantia nigra is increased bilaterally during circling.

Action Potentials↗
PubMed1989

Dopamine D1 heteroreceptors on striatonigral axons are not stimulated by endogeneous dopamine either tonically or after amphetamine: evidence from terminal excitability.

The role of dopamine D1 heteroreceptors located on the axon terminals of striatonigral neurons was investigated. Local infusion of the direct acting, specific dopamine D1 agonist, R-SKF 38393, into the substantia nigra terminal field of antidromically identified neostriatal projection neurons decreased the electrical excitability of these axons. This effect was dose-dependent and could be partially reversed by subsequent infusion of the specific D1 antagonist, R-SCH 23390. In contrast, excitability was not affected by the systemic administration of SCH-23390 (0.3 and 0.6 mg/kg, iv), or the non-specific antagonist haloperidol (0.2 mg/kg, iv). Since activation of the D1 heterorecptors by R-SKF 38393 decreased excitability, the inability of these antagonists to modify excitability indicates that endogenous dopamine does not tonically activate these receptors. Systemic administration of the indirect acting agonist, amphetamine (1.0 and 5.0 mg/kg, iv) also failed to change terminal excitability suggesting that, even when unnaturally high levels of dopamine are released in the substantia nigra, endogenous dopamine does not affect neostriatal axons terminating in the substantia nigra. Thus it is unlikely that endogeneous dopamine modulates neostriatal control of the substantia nigra through these presynaptic terminal D1 heteroreceptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Modulation of dopaminergic terminal excitability by D1 selective agents.

The effect of the active R (+) enantiomer of the dopaminergic selective D1 agonist 1-Phenyl-2,3,4,5-tetrahydrol-(1H)-3-benzazepine-7,8-diol HCL (R-SKF 38393) was examined on the excitability of antidromically identified nigro-striatal dopaminergic neurons. Striatal infusions of R-SKF 38393 produced a decrease in terminal excitability, which was reversed by subsequent infusion of the Dopaminergic D1 selective antagonist R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-o l-HCL (SCH 23390). The actions of these D1 specific agents are localized to the terminal fields of the dopaminergic neurons and are not nonspecific effects on the axonal membrane since application along the axons of these cells in the medial forebrain bundle produced no change (R-SKF 38393) or only a slight decrease (SCH 23390) in excitability. The results suggest that the terminal excitability of antidromically identified nigro-striatal dopaminergic neurons can be modified with specific Dopamine D1 receptor agents via a receptor mediated mechanism. Previous studies from this laboratory have demonstrated that the electrical excitability of nigro-striatal dopaminergic terminals is reduced by the dopaminomimetics apomorphine and amphetamine and is increased by the dopamine antagonists haloperidol, fluphenazine and sulpiride (Groves, Fenster, Tepper, Nakamura, and Young 1981; Tepper, Nakamura, Young and Groves 1984). Since, with the exception of sulpiride, these compounds affect both the D1 and D2 subclasses of dopamine receptors, it can not be concluded from these reports, which, if only one, of these receptors mediates the effect on terminal excitability.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1987

Wire electrodes for chronic single unit recording of dopamine cells in substantia nigra pars compacta of awake rats.

Stainless steel wire electrodes of varying sizes and coated with different insulating materials were tested in order to find a flexible fine wire which would allow the recording of small cells in deep structures of the brain in unrestrained, awake rats. Our main interest is to record from cells of substantia nigra pars compacta during locomotion. We found that stress relieved 18 micron stainless steel wire doubly insulated with lacquer and Parylene C provided the impedance, physical size, and flexibility needed to record single units during intense motor behavior.

Animals↗