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G Mereu

Publications and source records attributed to G Mereu.

At least 37 records · Page 2Linked to original sources
PubMed1987

Preferential stimulation of ventral tegmental area dopaminergic neurons by nicotine.

The effect of intravenous (i.v.) nicotine on the single unit activity of midbrain dopamine (DA) neurons was studied in rats under either local or general anesthesia. Nicotine (50-500 micrograms/kg) produced a dose-related increase in the firing rate of nigral pars compacta DA cells (A9), up to 25% above baseline, irrespective of the preparation. The same range of doses was more than three times as effective on ventral tegmental area DA cells (A10) in rats paralyzed and given a local anesthetic. By contrast, the majority of these cells were temporarily depressed in deeply anesthetized animals. All of the above effects were reversed and prevented by i.v. mecamylamine suggesting the involvement of nicotine cholinergic receptors. Moreover, after nicotine-induced stimulation, low doses of i.v. apomorphine inhibited the firing rate similar to controls indicating that dopamine receptors are not directly involved in the nicotinic action. The results suggest that acute nicotine shares with other drugs of abuse the characteristic of being more effective in stimulating A10 than A9 neurons.

Action Potentials↗
PubMed1987

Failure of subchronic lisuride to modify A10 dopamine autoreceptors' sensitivity.

The concept that prolonged treatment with dopamine (DA) mimetics results in a subsensitivity of DA autoreceptors generally is accepted. However, the present study indicates that the administration of a rather specific DA-D2 agonist, lisuride hydrogen maleate (LIS), for one week (200 micrograms/kg/daily) failed to modify the sensitivity of DA autoreceptors of A10 neurons. Indeed, by using extracellular single unit recording in chloral hydrate-anesthetized rats, we observed that neither intravenous apomorphine nor microiontophoresis of DA changed their firing rate-depressant potency when it was estimated at 1 or 3 days after the last LIS injection. A possible interpretation of the results is that the subchronic stimulation of DA-D2 receptors activates an unknown compensatory mechanism which avoids the changes in their sensitivity. Alternatively, the possibility that LIS may also possess antagonistic properties for DA receptors, which might balance the D2 receptors activation, is discussed.

Action Potentials↗
PubMed1987

Different epileptogenic activities of murine and ovine corticotropin-releasing factor.

The behavioral and EEG effects of rat and ovine corticotropin releasing factor (r- and o-CRF) were compared. Both peptides were injected intracerebroventricularly into rats through chronically implanted cannulae. At the doses of 0.1 and 1 microgram both peptides activated the EEG and stimulated motor activity. At the dose of 10 micrograms they produced spiking activity. However, while o-CRF-induced spiking activity was present both in the hippocampus and in the cortical leads and was associated with generalized myoclonic movements, that induced by r-CRF was confined in the hippocampus and was not accompanied by myoclonic movements. Spiking activity induced by r-CRF was suppressed by verapamil, but was not influenced by naloxone.

Animals↗
PubMed1987

The beta-carboline ZK 93423 inhibits reticulata neurons: an effect reversed by benzodiazepine antagonists.

A novel beta-carboline with benzodiazepine-like properties has recently been synthesized. We compared the effect of the i.v. administration of this drug, ZK 93423, with diazepam on the activity of nigral pars reticulata neurons which are known to be very sensitive to the inhibitory effect produced by GABA-mimetics and benzodiazepines. ZK 93423 (0.05-1.0 mg/kg) inhibited reticulata cells in a dose-related manner up to the cessation of their activity. Since the maximal rate-inhibition elicited by diazepam (1.0 mg/kg) was some 55% of baseline, ZK 93423 showed a much greater potency. Moreover, the firing depression by ZK 93423 was prevented and reversed by two benzodiazepine receptor antagonists: Ro15-1788 and ZK 93426. However, the dosage of Ro15-1788 required for these actions was at least five times higher than that for the blockade of the diazepam effect. The results indicate that the beta-carboline agonist ZK 93423 decreases the activity of reticulata neurons more effectively than diazepam.

Action Potentials↗
PubMed1986

Responsiveness to 'autoreceptor' doses of apomorphine inversely correlated with the firing rate of dopaminergic A9 neurons: action of baclofen.

Supersensitivity of dopamine (DA) autoreceptors develops soon after acute treatments with baclofen or gamma-butyrolactone, two drugs which suppress DA neuronal firing. We have hypothesized that this effect might reflect a condition associated with the low firing rate of DA cells induced by such treatments rather than a long-term adaptive modification of DA receptor sensitivity. In this study we show that the degree of the intravenous apomorphine-induced inhibition of A9-DA neurons is inversely correlated to the basal firing rate of these neurons. When administered after baclofen, apomorphine further reduced DA cell activities in a manner proportional to the predrug firing rate, as in control rats. Since the minute doses of apomorphine which were used are thought to selectively activate DA autoreceptors, our finding may indicate that DA autoreceptor stimulation is more effective when the activity of the DA neurons is low, or it is decreased by drugs such as baclofen.

Animals↗
PubMed1985

Low doses of ethanol inhibit the firing of neurons in the substantia nigra, pars reticulata: a GABAergic effect?

The intravenous administration of relatively low doses of ethanol (0.25-2.00 g/kg) produced a dose-dependent inhibition of the firing rate of the neurons located in the substantia nigra, pars reticulata (PR neurons). This effect was eliminated both by picrotoxin and bicuculline, two blockers of gamma-aminobutyric acid (GABA) transmission, and potentiated by muscimol (a direct GABA agonist) and diazepam (a representative of the benzodiazepine class which facilitate GABA transmission). The specific benzodiazepine antagonist, Ro 15-1788, blocked the potentiating effect of diazepam on the ethanol effect but failed to antagonize ethanol-induced inhibition of the firing rate of the neurons. These results indicate that ethanol might inhibit the firing of PR neurons through a GABAergic mechanism. Moreover, since PR neurons are thought to exert an inhibitory control on nigral dopaminergic neurons, it is suggested that the depression of the activity of such inhibitory interneurons may be responsible for ethanol-induced stimulation of dopaminergic activity.

Animals↗
PubMed1985

Modulation of terminal excitability of mesolimbic dopaminergic neurons by D-amphetamine and haloperidol.

Electrophysiological techniques were used to study the changes in the terminal excitability of mesolimbic DA and non-DA neurons following the infusion of D-amphetamine (D-AMP) and haloperidol (HAL) into the nucleus accumbens (NAc) of rats. The amount of current needed to evoke antidromic spikes by electrical stimulation of the NAc was used as an index of the excitability of axon terminals of these neurons. The excitability of DA neurons was decreased by D-AMP and increased by HAL. In addition, the effect produced by D-AMP was reversed by HAL. By contrast, these drugs either induced an opposite effect or were ineffective in inducing changes on the excitability of nerve terminals of mesolimbic non-DA neurons. Infusion of the vehicle or saline produced no effect. D-AMP and HAL were still effective in modulating the excitability of mesolimbic DA nerve terminals after the destruction of NAc neurons by ibotenic acid. The results suggest that the effects seen after D-AMP and HAL are mediated primarily by DA autoreceptors. It is likely that the increase in the current needed for evoking antidromic spikes after infusion of D-AMP into the terminal region is the consequence of DA autoreceptor-mediated hyperpolarization of terminal membranes. On the other hand, HAL could exert its actions by blocking autoreceptor-mediated hyperpolarization.

Animals↗
PubMed1985

Low doses of ethanol activate dopaminergic neurons in the ventral tegmental area.

In unanesthetized rats the intravenous administration of low doses of ethanol (0.125-0.5 g/kg) produced a dose-dependent increase (30-80%) in the firing rate of dopaminergic (DA) neurons in the Ventral Tegmental Area (VTA). In agreement with previous observations, a dose range between 0.5 and 2 g/mg of ethanol was needed to produce comparable stimulant responses in DA neurons of the Substantia Nigra Pars Compacta. However, in anesthetized rats, doses of ethanol up to 1 g/kg failed to activate VTA-DA neurons. The high sensitivity of VTA-DA neurons to ethanol activation suggests that they might be involved in the reinforcing properties of the drug.

Animals↗
PubMed1985

SCH 23390, a selective D1 dopamine receptor blocker, enhances the firing rate of nigral dopaminergic neurons but fails to activate striatal tyrosine hydroxylase.

The intraperitoneal administration of SCH 23390, a selective D1 receptor antagonist, produced catalepsy and increased the firing rate of dopamine (DA) neurons in the substantia nigra (SN-DA neurons). Maximal increase (110%) was of the same magnitude as that produced by a supramaximal dose of haloperidol, which produced no additional activation over that produced by SCH 23390. Contrary to haloperidol, SCH 23390 failed to increase the affinity of tyrosine hydroxylase (TH) for the pteridine cofactor and produced only a modest increase (30%) in DA synthesis. Moreover, SCH 23390 did not prevent haloperidol-induced activation of either TH or DA synthesis. It is concluded that blockade of postsynaptic D1 receptors results in the stimulation of SN-DA neurons, but this effect fails to activate TH and DA synthesis unless presynaptic DA autoreceptors are blocked.

Animals↗
PubMed1985

SCH 23390, a selective dopamine D1 antagonist, activates dopamine neurons but fails to prevent their inhibition by apomorphine.

SCH 23390, a rather selective D1 receptor blocker, activates the firing rate of dopamine (DA) neurons in the substantia nigra (SN-DA neurons) in rats, similarly to haloperidol (a D1-D2 receptor antagonist) and sulpiride (a selective D2 receptor blocker). These neuroleptics produce no additional increase over the maximal activation produced by SCH 23390. Unlike haloperidol or sulpiride, SCH 23390 fails to prevent the inhibition by apomorphine of SN-DA neurons, a DA autoreceptor-mediated effect. It is suggested that the doses of SCH 23390 that stimulate DA neurons block D2 in addition to D1 receptors, or that D1 blockade results in the functional inactivation of a specific population of D2 receptors as well. The failure of SCH 23390 to block the apomorphine effect indicates that DA autoreceptors can be pharmacologically differentiated form postsynaptic DA receptors.

Action Potentials↗
PubMed1985

Sedation and sleep induced by high doses of apomorphine after blockade of D-1 receptors by SCH 23390.

The effect of SCH 23390, a selective blocker of D-1 receptors, on apomorphine-induced behavioural and EEG changes was studied in rats. In control rats, a low dose of apomorphine (50 micrograms/kg s.c.) produced sedation associated with EEG synchronization. A high dose of apomorphine (1 mg/kg s.c.) produced stereotypy associated with EEG desynchronization. At the dose of 1 mg/kg i.p., SCH 23390 decreased motor activity but failed to alter the EEG pattern. The administration of either the low or high dose of apomorphine to SCH 23390-treated rats elicited a marked sedative response associated with EEG synchronization. The EEG synchronization produced by apomorphine (50 micrograms/kg) in SCH 23390-treated rats was prevented by (-)-sulpiride (25 mg/kg i.p.), a D-2 receptor blocker. It is concluded that by preventing the excitatory response to apomorphine SCH 23390 discloses the existence of a population of D-2 receptors mediating sedation and sleep.

Animals↗
PubMed1985

Zetidoline, a novel neuroleptic, activates nigral dopaminergic neurons in rats.

Zetidoline (ZET), a rather selective dopamine (DA) D2-receptor blocker, was found to be equipotent to haloperidol and over 300 times as potent as sulpiride in activating the firing rate of substantia nigra dopaminergic neurons (SN-DA neurons) in unanesthetized rats. Moreover, like classic and atypical neuroleptics, ZET reversed and prevented apomorphine-induced inhibition of SN-DA neurons.

Animals↗
PubMed1984

Ethanol stimulates the firing rate of nigral dopaminergic neurons in unanesthetized rats.

In unanesthetized paralyzed rats, i.v. ethanol administration (0.5-2.0 g/kg) increased (by 30-120%) the firing rate of dopaminergic (DA) neurons in the substantia nigra, pars compacta. Doses of 4.0 g/kg or higher produced an initial stimulation followed by a long-lasting inhibition of firing. On the contrary, in rats anesthetized with halothane (2.5% v/v in air) or with chloral hydrate (400 mg/kg), doses of ethanol up to 2 g/kg failed to activate DA neurons, while a dose of 4 g/kg inhibited neuronal firing without the initial stimulant response. In unanesthetized-curarized rats, the i.v. administration of either chloral hydrate (100-400 mg/kg) or pentobarbital (10-40 mg/kg) or the inhalation of halothane (0.5-2.5% v/v in air) produced a dose-dependent increase in the firing rate of DA neurons. However, the maximum increase produced by these anesthetics was less pronounced and shorter lasting than that produced by ethanol.

Action Potentials↗
PubMed1983

beta-Carbolines activate neurons in the substantia nigra pars reticulata: an effect reversed by diazepam and Ro15-1788.

Diazepam (0.5 mg/kg i.v.) was found to inhibit the firing rate of substantia nigra pars reticulata (SN-PR) cells by 50%. In contrast, beta-CCM, at the doses of 125 and 250 micrograms/kg i.v. increased the firing rate by 90 and 150%, respectively, while DMCM produced similar increases at doses of 250 and 500 micrograms/kg i.v. Both beta-carboline-induced excitation and diazepam-induced inhibition were reversed to baseline values by the specific antagonist of benzodiazepine recognition sites, Ro15-1788 (2.0 mg/kg i.v.). Moreover, the stimulant effect of beta-carbolines was also reversed by diazepam (1.0 mg/kg) to about 50% of baseline. The results indicate that beta-carbolines specifically influence the activity of SN-PR cells through a mechanism opposite to that of benzodiazepines themselves, acting on benzodiazepine recognition sites.

Animals↗
PubMed1983

(-)-Sulpiride activates the firing rate and tyrosine hydroxylase activity of dopaminergic neurons in unanesthetized rats.

The effect of i.v. sulpiride on the firing rate of dopaminergic neurons in the substantia nigra, pars compacta (SN-DA cells) and tyrosine hydroxylase (TH) activity in the caudate nucleus was studied. In rats, paralyzed with succinylcholine and artificially respirated, (-)-sulpiride (10-50 mg/kg) produced a dose-related increase in the firing rate of SN-DA cells and in TH activity. On the contrary, in rats anesthetized with halothane, (-)-sulpiride (up to 50 mg/kg) activated neither dopaminergic firing nor TH activity. However, (-)-sulpiride (10-25 mg/kg) readily reversed the inhibitory effect of i.v. apomorphine (25 micrograms/kg) on dopaminergic firing in both anesthetized and unanesthetized rats. Since sulpiride fails to inhibit DA-sensitive adenylate cyclase, it may be concluded that DA receptors, whose blockade results in increased dopaminergic firing and TH activation, are not coupled with this enzyme. Moreover, the results indicate that the mechanism responsible for firing and TH stimulation is inhibited by halothane anesthesia. The latter significantly decreased also the stimulant effect of i.v. haloperidol on striatal TH activity.

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