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S Arbilla

Publications and source records attributed to S Arbilla.

At least 55 records · Page 3Linked to original sources
PubMed1985

Trace amines inhibit the electrically evoked release of [3H]acetylcholine from slices of rat striatum in the presence of pargyline: similarities between beta-phenylethylamine and amphetamine.

Amphetamine (AMPH) inhibits the electrically evoked release of [3H]acetylcholine (ACh) from rat striatal slices through the activation of inhibitory dopamine receptors. Naturally occurring analogs of amphetamine (AMPH) such as beta-phenylethylamine (beta-PEA), tyramine (TYR) and octopamine (OCT) are present in trace amounts in the brain of several species. We have studied in this model, in comparison with AMPH, the effects of beta-PEA, TYR and OCT, in order to explore if their central effects are mediated through an action involving dopaminergic nerve terminals or whether they activate a specific receptor directly. In contrast to the results obtained with AMPH, in the absence of inhibition of monoamine oxidase activity, the three amines beta-PEA (0.1-10 microM), TYR (0.1-10 microM) and OCT (10 microM) did not affect the electrically evoked release of [3H]ACh. On the other hand, in the presence of pargyline (10 microM), the three amines inhibited the electrically evoked release of [3H]ACh and all subsequent experiments were carried out in the presence of pargyline. After pretreatment with reserpine (5 mg/kg s.c., 24 h), which results in a 95% depletion of the endogenous dopamine content, OCT lost its inhibitory effect on [3H]ACh release, whereas beta-PEA and TYR still inhibited the electrically evoked release of [3H]ACh. Reserpine pretreatment (5 mg/kg s.c., 24 h) combined with alpha-methyl-p-tyrosine (300 mg/kg i.p., 2 h) reduced endogenous dopamine levels by 99.9%, but, under these conditions, beta-PEA, TYR and AMPH still retained their inhibitory effect on [3H]ACh, release. These inhibitory effects of beta-PEA and AMPH on [3H] ACh release were antagonized by S-sulpiride (0.1 microM). In striatal slices from untreated rats, the inhibition of [3H]ACh released by beta-PEA (30 microM), TYR (30 microM) or AMPH (10 microM) was abolished completely after a 6-hydroxydopamine lesion of the nigro-striatal dopaminergic system. The present data indicate that in order to inhibit the release of [3H]ACh from rat striatal slices in vitro, OCT requires the integrity of vesicular stores of dopamine. On the other hand, beta-PEA, TYR and AMPH are still active when the dopamine levels are depleted, although they require the integrity of the dopaminergic nerve terminal. Inhibition of monoamine oxidase is essential to demonstrate the inhibitory effects of exogenous beta-PEA, TYR and OCT on cholinergic transmission. Our results indicate that a hypothesis concerning a possible physiopathological role of endogenous beta-PEA or TYR should involve concomitant changes in monoamine oxidase activity.

Acetylcholine↗
PubMed1984

Differential effects of the stereoisomers of 3PPP on dopaminergic and cholinergic neurotransmission in superfused slices of the corpus striatum.

The two enantiomers of 3PPP were tested on the spontaneous and electrically-evoked release of 3H-dopamine from slices of the rabbit caudate nucleus and of 3H-acetylcholine (3H-ACh) from slices of the rat caudate nucleus. In caudate slices labelled with 3H-dopamine, exposure to (+)3PPP (0.1-1 microM) facilitated the spontaneous outflow of radioactivity with a concomitant inhibition of the electrically-evoked release of 3H-dopamine. In the presence of cocaine 10 microM, exposure to (+)3PPP (1 microM) inhibited the electrically evoked release of 3H-dopamine without modifying the spontaneous outflow of radioactivity. This inhibitory effect was not significantly antagonized by S-sulpiride 0.01 microM. Exposure to (+)3PPP 1 microM inhibited the electrically-evoked release of 3H-ACh, and this effect was not modified by pretreatment with reserpine alone, or in combination with alpha-methyl-p-tyrosine (alpha-MT). In contrast to the (+) enantiomer, exposure to (-)3PPP (0.1-1 microM) facilitated the electrically-evoked release of 3H-dopamine without affecting the spontaneous outflow of radioactivity. (-)3PPP antagonized the inhibitory effect of apomorphine on the electrically-evoked release of 3H-dopamine. Exposure to (-)3PPP 1 microM did not modify the spontaneous or the electrically-evoked release of 3H-ACh. Yet, this concentration of (-)3PPP antagonized significantly the inhibitory effect of 0.03 microM apomorphine, 1 microM d-amphetamine, and 1 microM (+)3PPP on the electrically-evoked release of 3H-ACh (-)3PPP (0.1-1 microM) was about 100 times less potent than S-sulpiride at antagonizing the inhibitory effect of apomorphine on the electrically-evoked release of 3H-ACh.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1983

Amphetamine enhances latent dopaminergic neurotransmission in the rat striatum. Effects on 3H-acetylcholine release.

The electrically evoked, calcium-dependent release of 3H-acetylcholine from slices of rat striatum was inhibited in a concentration-dependent manner by (+)-amphetamine (0.2-20 microM). This inhibitory effect of (+)-amphetamine was unaffected by depletion of the endogenous stores of dopamine by pretreatment with reserpine (5 mg/kg, 24 h). However, the combined treatment of reserpine with alpha-methyl-p-tyrosine (300 mg/kg) or NSD 1015 (100 mg/kg) reduced significantly these inhibitory effects of (+)-amphetamine. Similar results were obtained after chronic 6-hydroxydopamine lesions of the corpus striatum. The inhibition of 3H-acetylcholine release by (+)-amphetamine in rats pretreated with reserpine was potentiated in the presence of 10 microM pargyline. These results support the view that the inhibitory effects of (+)-amphetamine on the electrically-evoked release of 3H-acetylcholine are mediated by dopamine released from a special pool of newly synthetized transmitter rather than through a direct action on an amphetamine recognition site or receptor.

Acetylcholine↗
PubMed1983

Amphetamine inhibits the electrically evoked release of [3H]dopamine from slices of the rabbit caudate.

The effects of d-amphetamine on the spontaneous and electrically evoked release of [3H]dopamine in slices of the rabbit caudate nucleus were investigated. At a concentration of 0.1 microM amphetamine did not modify the spontaneous outflow of radioactivity, but significantly inhibited the release of [3H]dopamine elicited by electrical stimulation. At a 10-fold higher concentration (1 microM) amphetamine enhanced the spontaneous outflow of radioactivity and also inhibited the stimulation-evoked release of [3H]dopamine. The inhibition by amphetamine of electrically evoked release of [3H]dopamine was also observed under conditions in which monoamine oxidase was inhibited by pargyline. At concentrations of 0.1 and 0.5 microM amphetamine there was no inhibition of neuronal uptake and retention of [3H]dopamine in slices of the rabbit caudate. In the presence of 100 microM l-3-iodotyrosine, the inhibition by amphetamine of [3H]dopamine release was still obtained. The dopamine receptor antagonists, haloperidol and sulpiride, were not able to antagonize the inhibition by amphetamine of the electrically evoked release of [3H] dopamine at concentrations which effectively blocked apomorphine-induced inhibition of stimulation-evoked release of the labeled neurotransmitter. Exposure to serotonin in the presence of an inhibitor of neuronal uptake did not modify the spontaneous outflow of radioactivity or the electrically evoked release of [3H] dopamine. Nomifensine, an inhibitor of neuronal uptake of dopamine prevented the release of [3H]dopamine induced by exposure to 10 microM amphetamine and antagonized the inhibitory effects of lower concentrations of amphetamine on the electrically evoked release of [3H]dopamine. Tyramine and amfonelic acid in low concentrations enhanced the spontaneous outflow of radioactivity and, similarly to amphetamine, inhibited the electrically evoked release of [3H]dopamine. Exposure to bretylium (1 and 10 microM) inhibited the release of [3H]dopamine elicited by electrical stimulation. In the presence of bretylium, the inhibition by amphetamine of the stimulation-evoked release of [3H]dopamine was still present. In contrast to its inhibitory action on the release of [3H]dopamine, exposure to amphetamine (0.1-1.0 microM) enhanced in a concentration-dependent manner the electrically evoked release of [3H]norepinephrine from the rabbit hypothalamus. These results indicate that the inhibition by amphetamine of the electrically evoked release of [3H]dopamine does not involve the activation of presynaptic inhibitory dopamine autoreceptors possibly located on dopaminergic nerve terminals.(ABSTRACT TRUNCATED AT 400 WORDS)

Amphetamine↗
PubMed1983

Changes in sensitivity of release modulating dopamine autoreceptors after chronic treatment with haloperidol.

The release of recently taken up [3H]dopamine ([3H]DA) elicited by electrical stimulation (3 Hz, 2 min, 16 mA) from slices of the rabbit caudate nucleus is inhibited by apomorphine (0.01-0.1 microM) in a concentration-dependent manner. This action is mediated through the activation of presynaptic inhibitory DA autoreceptors. The inhibition of [3H]DA release by apomorphine (0.1 microM) was antagonized 2 hr, but not 24 hr after the single administration of haloperidol (1 mg/kg s.c.). After 2 days of withdrawal after 28 days of chronic treatment with haloperidol (1 mg/kg s.c.) once daily, apomorphine (0.01-0.1 microM) was more effective in inhibiting [3H]DA release elicited by electrical stimulation when compared with rabbits injected chronically with either the vehicle for haloperidol or with saline. In superfused slices of the rabbit caudate nucleus, exposure to S-sulpiride (0.1 and 1 microM) increased in a concentration-dependent manner the release of [3H] DA elicited by electrical stimulation. After 28 days of chronic treatment with haloperidol, the facilitation of [3H]DA release by S-sulpiride was significantly reduced when compared with the controls. The inhibition of central noradrenergic transmission by DA receptor agonists was studied in hypothalamic slices prelabeled with [3H]norepinephrine ([3H-NE]). Apomorphine (0.01-1 microM) inhibited the electrically evoked (5 Hz, 2 min, 26 mA) release of [3H]NE from hypothalamic slices of untreated rabbits. The sensitivity to the inhibitory effect of apomorphine on [3H]NE overflow remained unaffected after 2 days of withdrawal following 28 days of chronic treatment with haloperidol. In summary, our results indicate that chronic haloperidol administration induces changes in sensitivity of the DA autoreceptors regulating dopaminergic neurotransmission but does not affect the sensitivity of DA receptors modulating NE release in the central nervous system. These results suggest that the DA autoreceptors that regulate dopaminergic neurotransmission may play a physiological role in the modulation of transmitter release and consequently are susceptible to the development of changes in sensitivity after chronic receptor blockade. The possible implication of changes in sensitivity of the DA autoreceptor during the treatment of schizophrenia with neuroleptics is discussed.

Animals↗
PubMed1982

Concomitant decrease in [3H]imipramine binding in cat brain and platelets after chronic treatment with imipramine.

Cats were treated chronically with imipramine (7.5 mg/kg i.p. twice daily for 20 days). Maximal [3H]dihydroalprenolol binding was reduced in the cerebral cortex of the treated animals whereas maximal [3H]spiroperidol binding to 5HT2-receptors was unchanged. Maximal [3H]imipramine binding was decreased to a similar extent in both hypothalamus and platelets of the same animals. This parallel decrease in [3H]imipramine binding in brain and platelets is discussed in relation to the lower [3H]imipramine binding found in platelets from untreated depressed patients as compared to those from control volunteers.

Animals↗
PubMed1982

Noradrenergic neurotransmission in the brain of a convulsive mutant mouse, differences between the cerebral cortex and the brain stem.

The Quaking mouse is a genetically determined model of convulsive disorders. We investigated the modulation of noradrenergic neurotransmission through alpha 2-adrenoceptors in the occipital cortex and the brain stem of this mutant. The endogenous levels of noradrenaline were similar in the cerebral cortex of the Quaking mice and their corresponding controls, while a significant increase of endogenous noradrenaline was found in the brain stem of the mutants. The rate of disappearance of noradrenaline in the cerebral cortex and the brain stem after injection of FLA 63 was identical in control and Quaking mice. The calcium-dependent electrically evoked overflow of 3H-noradrenaline from slices of occipital cortex was inhibited by clonidine and enhanced by yohimbine in Quaking as well as in normal mice. The negative feed-back mechanism mediated by presynaptic alpha 2-adrenoceptors operates to a similar extent in both strains of mice. In contrast to the occipital cortex, in the brain stem, the amount of neurotransmitter released by electrical stimulation was significantly increased in Quaking mice when compared with controls. However, in the brain stem, the negative feed-back regulation of noradrenaline release operates to a similar extent in both strains of mice. When the endogenous levels of MOPEG were determined in the brain stem, they were found to be significantly higher in the Quaking mice when compared to the controls. The results suggest that an increase in noradrenergic neurotransmission in the brain stem, rather than in the cerebral cortex, could contribute to the behavioural abnormalities exhibited by the Quaking mice.

Animals↗
PubMed1982

gamma-Aminobutyric acid (GABA) receptor stimulation. II. Specificity of progabide (SL 76002) and SL 75102 for the GABA receptor.

Progabide and its immediate metabolite SL 75102 displace [3H]gamma-aminobutyric acid (GABA), [3H]muscimol and [3H]isoguvacine from their binding sites to membranes prepared from rat brain or human cerebellum and increase (SL 75102) [3H]flunitrazepam binding to rat cerebral cortex membranes. In contrast, these compounds have very weak or no effects on alpha or beta noradrenergic, histamine, muscarinic cholinergic or glycine receptors or on the [3H]imipramine or [3H]kainate binding sites. Neither progabide nor SL 75102 inhibit GABA synthesis, metabolism or uptake. Also, the uptake of norepinephrine, serotonin and dopamine into synaptosomes of cerebral regions is not affected by progabide. [3H]GABA release from substantia nigra slices is decreased by SL 75102 and progabide, in agreement with the hypothesis of a GABAergic autoreceptor controlling GABA release from its nerve terminals. These data suggest a specific agonist action of progabide and SL 75102 on GABA receptors.

Animals↗
PubMed1981

Stereoselectivity of presynaptic autoreceptors modulating dopamine release.

The effects of the (R)- and (S)-enantiomers of sulpiride and butaclamol were studied on the spontaneous and field stimulation-evoked release of total radioactivity from slices of rabbit caudate nucleus prelabelled with [3H]dopamine. (S)-Sulpiride in concentrations ranging from 0.01--1 microM enhanced the electrically evoked release of [3H]dopamine while (R)-sulpiride was 10 times less potent than (S)-sulpiride. Exposure to (S)-butaclamol (0.01--1 microM) but not to (R)-butaclamol (0.1--10 microM) enhanced the field-stimulated release of [3H]dopamine. The facilitatory effects of (S)- and (R)-sulpiride and (S)-butaclamol on the stimulated release of the labelled neurotransmitter were observed under conditions in which these drugs did not modify the spontaneous outflow of radioactivity. Only the active enantiomers of sulpiride and butaclamol antagonized the inhibition by apomorphine (1 microM) of the stimulated release of [3H]dopamine. Our results indicate that the presynaptic inhibitory dopamine autoreceptors modulating the stimulation-evoked release of [3H]dopamine in the caudate nucleus are, like the classical postsynaptic dopamine receptors, chemically stereoselective.

Animals↗
PubMed1981

Dopamine receptor mediated inhibition by pergolide of electrically-evoked 3H-dopamine release from striatal slices of cat and rat: slight effect of ascorbate.

The dopamine receptor agonist pergolide inhibited the calcium-dependent, electrically evoked overflow of tritium from slices of the striatum of cat or rat prelabelled with 3H-dopamine. This inhibition of tritium overflow by nanomolar concentrations of pergolide was antagonized by the benzamide neuroleptic S-sulpiride (0.1 microM). In millimolar concentrations, L- ascorbate had slight or no effects on this dopamine receptor mediated inhibition, in striatal slices of either the cat or the rat. Since these same concentrations of ascorbate have been reported to completely block the specific binding of 3H-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN) and of 3H-apomorphine to presumed dopamine receptors, the present results suggest a dissociation between the characteristics of 3H-ADTN and 3H-apomorphine binding and the dopamine autoreceptor. Previous contradictory results concerning the existence of inhibitory dopamine receptors which modulate depolarization-evoked overflow of dopamine from the striatum of the rat are thus apparently not due to a species difference nor to the use of ascorbate, but rather to differences in experimental conditions.

Animals↗
PubMed1981

Inhibition by apomorphine of the potassium-evoked release of [3H]-gamma-aminobutyric acid from the rat substantia nigra in vitro.

1 The spontaneous and potassium-evoked release of tritium from the rat substantia nigra prelabelled with [(3)H]-gamma-aminobutyric acid [(3)H]-GABA were assessed in vitro under conditions of superfusion.2 Kainic acid lesions performed in the right caudate nucleus resulted in a 70% reduction in the ability of the homolateral nigral cells to take up and retain [(3)H]-GABA when compared with the unlesioned side. The potassium-evoked release of [(3)H]-GABA remained proportional to the radioactivity retained in the tissue suggesting that the nigral GABA neurones that survived kainic acid treatment were still functional.3 The spontaneous outflow of [(3)H]-GABA was significantly increased by exposure to different concentrations of exogenous GABA (10 to 1000 muM) when amino-oxyacetic acid was present in the incubation medium.4 Apomorphine in concentrations ranging from 1 to 30 muM inhibited the calcium-dependent release of [(3)H]-GABA induced by 1 min exposure to 30 mM K(+). These concentrations of apomorphine did not affect the spontaneous outflow of radioactivity. In vivo administration of haloperidol 0.2 mg/kg antagonized the in vitro inhibition by apomorphine of the K(+)-evoked release of [(3)H]-GABA.5 The results obtained with apomorphine and haloperidol suggest the presence of presynaptic dopamine-like inhibitory receptors in gabaergic nerve terminals.6 Dopamine in concentrations ranging up to 300 muM did not modify either the spontaneous or the K(+)-evoked release of [(3)H]-GABA from the substantia nigra. These concentrations of dopamine effectively displaced [(3)H]-dopamine recently taken up into the substantia nigra.7 Our results do not support the view that dendritic release of dopamine from the substantia nigra might be involved in the physiological modulation of the spontaneous or the stimulation-evoked release of GABA.

Animals↗
PubMed1981

Presynaptic receptors and modulation of the release of noradrenaline, dopamine and GABA.

A review of the role of presynaptic receptors in the modulation of neurotransmitter release indicates two types of presynaptic receptors. By means of presynaptic inhibitory autoreceptors a neurotransmitter can regulate its own release. In addition, presynaptic receptors are acted upon by other endogenous compounds, either transmitters released from adjacent nerve terminals, blood-borne compounds or locally-formed substances, involved in trans-synaptic feed-back. Both types of presynaptic receptors may be involved in the physiological control of transmitter release and are the target of drug action, either as agonists or as antagonists.

Adenosine↗
PubMed1980

Rapid-eye-movement sleep deprivation decreases the density of 3H-dihydroalprenolol and 3H-imipramine binding sites in the rat cerebral cortex.

The high affinity binding sites for 3H-imipramine (3H-IMI) and 3H-dihydroalprenolol (3H-DHA) in the rat cerebral cortex were studied after 2,4 48 and 72 h of rapid-eye-movement (REM) sleep deprivation. Both the Kd and Bmax values for 3H-IMI and 3H-DHA binding remained unaffected after 24 or 48 h of REM sleep deprivation. After 72 or REM sleep deprivation there was a significant reduction in the Bmax for 3H-IMI and 3H-DHA binding with a concomitant increase in the apparent affinities. The reduction in high affinity 3H-IMI and 3H-dihydroalprenolol binding sites observed 72 h after REM sleep deprivation could be related to the antidepressant effects of REM sleep deprivation in man.

Alprenolol↗
PubMed1980

Delay by bretylium of adrenergic nerve degeneration after sympathectomy of the submaxillary gland.

Administration of 24 mumol/kg of bretylium 10 h after ganglionectomy delayed the loss of endogenous norepinephrine and the impairment of neuronal uptake of 3H-metaraminol (3H-MA) that follow sympathetic denervation. This delay was evident 16 and 20 h after denervation. Twenty four h after ganglionectomy, when NE stores and uptake of 3H-MA were reduced to their lowest values in untreated rats, in bretylium-treated ones these values were approximately 40% of those in normal glands. The onset of degeneration secretion in treated rats was delayed by about 9 h. The development of prejunctional supersensitivity was also delayed. The subcellular distribution of NE in normal and 16 h denervated glands showed that denervation reduced the neurotransmitter to the same extent in the 3 fractions: coarse, supernatant and microsomal. Treatment with bretylium and pargyline prevented the loss of NE from the microsomal fraction. Previous administration of pargyline antagonized the protection of 3H-MA uptake seen in 28 h denervated rats treated with bretylium. However, this drug combination induced a greater retention of endogenous NE 24 h after denervation. Bretylium inhibited intraneuronal MAO by 40%. It is concluded that bretylium treatment can delay the degeneration of adrenergic nerve terminals separated from the cell bodies by a pharmacological effect probably not related to MAO inhibition or to its neurone blocking action.

Animals↗
PubMed1980

Chronic sympathetic denervation increases muscarinic cholinoceptor binding in the rat submaxillary gland.

Superior cervical ganglionectomy was found to produce a large decrease in the cocaine-sensitive accumulation of 3H-noradrenaline in the rat submaxillary gland, indicating an effective sympathetic denervation. Six weeks after unilateral denervation the muscarinic cholinoceptor binding of 3H-QNB was increased by over 50% compared to the contralateral, innervated gland. There were no differences in the Kd values between the innervated and denervated glands. These results suggest that changes in muscarinic cholinoceptor density might be in part responsible for the postsynaptic supersensitivity to cholinoceptor agonists observed after chronic sympathetic denervation.

Animals↗