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Y Michotte

Publications and source records attributed to Y Michotte.

At least 37 records · Page 2Linked to original sources
PubMed2000

Serotonin reuptake inhibition by citalopram in rat strains differing for their emotionality.

Acute administration of the selective serotonin (5-HT) reuptake inhibitor (SSRI), citalopram (1-10 mg/kg, i.p. 1 h before an elevated plus-maze test), to Spontaneously Hypertensive rats (SHRs), Lewis (LEW) rats, and Wistar-Kyoto (WKY) rats, i.e., rat strains differing for their emotionality, promoted anxiety, and/or hypoactivity, except in WKY rats. In the three strains, such a pretreatment increased central 5-HT levels and/or decreased 5-hydroxyindoleacetic acid levels. Hippocampal, but not midbrain or striatal, [3H]citalopram binding at 5-HT transporters was lower in WKY rats than in SHRs. However, neither [3H]5-HT reuptake kinetics nor the potencies of citalopram (1-1000 nM) to inhibit [3H]5-HT reuptake into hippocampal and striatal synaptosomes differed between strains. This was confirmed in vivo by means of microdialysis in the hippocampus of freely moving rats. Thus, although LEW rats displayed a 3-4 fold higher baseline level of extracellular 5-HT in the hippocampus, compared with SHRs and WKY rats, local perfusion with 1 microM citalopram promoted relative increases in extracellular 5-HT levels over baseline that were similar in all strains. Lastly, acute i.p. administration of 3.3 mg/kg citalopram (1 h beforehand) decreased to similar extents [3H]5-HT reuptake into hippocampal synaptosomes from SHRs and WKY rats. This study indicates that genetic differences in the behavioural responses to SSRIs may involve 5-HT transporter-independent mechanisms.

Animals↗
PubMed2000

In vivo study of the effect of valpromide and valnoctamide in the pilocarpine rat model of focal epilepsy.

PURPOSE: We evaluated the effectiveness of the commonly used antiepileptic drug sodium valproate (400 mg/kg) and two of its amide derivatives, valpromide and valnoctamide (both 100 mg/kg), in an in vivo rat model of focal epilepsy. Our main interest was to get insight into possible changes in extracellular amino acid neurotransmitter levels following administration of the drugs, both in control and in epileptic conditions. METHODS: Seizures were evoked in freely moving rats by intrahippocampal administration of pilocarpine via a microdialysis probe (10 mM for 40 min at 2 microl/min). Microdialysis was also used as in vivo sampling technique and alterations in extracellular hippocampal glutamate and GABA levels were monitored. Electrophysiological evidence for the presence or absence of seizures was simultaneously recorded with electrocorticography. RESULTS: The focally evoked pilocarpine-induced seizures were completely prevented by acute intraperitoneal pretreatment with each of the three drugs in the respective doses. Effective protection was reflected in the electrocorticographic recordings and in the lack of sustained elevations of the extracellular glutamate levels after pilocarpine perfusion. Little effects were seen on the basal extracellular amino acid levels after systemic administration of each of the compounds, nor after the intrahippocampal administration of sodium valproate. CONCLUSIONS: Valnoctamide and valpromide (100 mg/kg) proved to be at least as effective as their parent compound sodium valproate (400 mg/kg) against pilocarpine-induced seizures. All three compounds however failed to induce significant initial alterations in extracellular hippocampal GABA release. This questions the enhancement of GABA-mediated inhibition as being one of their mechanisms of action.

Amides↗
PubMed1999

Effects of diazepam on extracellular brain neurotransmitters in pilocarpine-induced seizures in rats.

The present study was undertaken to gain insights into the mechanism of action of diazepam in focally-evoked pilocarpine-induced seizures by concomitantly assessing the changes produced in the extracellular levels of glutamate, GABA (gamma-aminobutyric acid) and dopamine. In vivo microdialysis, coupled to continuous monitoring of electrocorticographic (ECoG) recordings, was performed in freely moving rats. Intrahippocampal perfusion with 10 mM pilocarpine (40 min, 2 microl/min) produced limbic seizures. A single dose of intraperitoneal diazepam (5 mg/kg) was administered 2 h after pilocarpine perfusion was started. Dialysates were sampled both from hippocampus and cerebellum and analysed by microbore liquid chromatography. Diazepam produced instant inhibition of behavioural and ECoG seizure activity. Pilocarpine-induced increases in the extracellular levels of glutamate and dopamine in hippocampus were promptly reduced by diazepam. No concurrent alterations in pilocarpine-induced increases in the extracellular levels of GABA in either hippocampus or cerebellum were seen. Pilocarpine enhanced cerebellar glutamate levels only transiently and levels returned to baseline before diazepam administration. No further changes in cerebellar glutamate levels were observed with diazepam. Our findings suggest that the anti-convulsant action of diazepam against pilocarpine-induced seizures is associated with a prompt attenuation of extracellular hippocampal glutamate overflow without concurrent alteration of pilocarpine-induced increases in endogenous GABA levels. Diazepam also significantly decreased pilocarpine-induced increases in extracellular dopamine levels within the hippocampus. No immediate alterations of the basal levels of the neurotransmitters monitored were observed with diazepam.

Animals↗
PubMed1998

Effect of trihexyphenidyl, a non-selective antimuscarinic drug, on decarboxylation of L-dopa in hemi-Parkinson rats.

In vivo microdialysis was used to study the effect of the non-selective muscarinic antagonist, trihexyphenidyl, on the decarboxylation of levodopa (L-dopa) in the striatum of hemi-Parkinson rats. In normal rats, continuous perfusion of trihexyphenidyl (1 mM) via the microdialysis probe induced a significant increase in striatal dopamine release, followed by a decrease to below baseline values. A similar effect was observed, though less pronounced, in denervated striatum of rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway. In these hemi-Parkinson rats, continuous striatal perfusion of trihexyphenidyl had no effect on the biotransformation of locally applied L-dopa (2 microM for 20 min) to dopamine in either intact or denervated striatum. However, systemic administration of trihexyphenidyl (1.5 mg/kg i.p.) produced an attenuation of the L- dopa-induced dopamine release in the intact striatum (contralateral to the lesion) of hemi-Parkinson rats. This effect was absent in the denervated striatum of these animals. We confirmed that L-dopa induces an increase in striatal dopamine output which is influenced by the severity of the dopaminergic denervation. The absence of an effect of trihexyphenidyl locally applied in the striatum, on biotransformation of L-dopa suggests that the site of action of antimuscarinic drugs may not be in the striatum and, therefore, remains unclear. The mechanism of action of these drugs is not well understood but appears more complicated than previously thought.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Dopaminergic regulation of serotonin release in the substantia nigra of the freely moving rat using microdialysis.

The functional regulation by dopamine (DA) receptors of serotonin (5-HT) release from the rat substantia nigra (SN) was investigated using in vivo microdialysis. A D1- and D2-receptor-mediated inhibition of nigral 5-HT release was demonstrated in this study. Continuous administration of the D1-receptor agonist CY 208243 (10 microM) through the probe did not alter extracellular DA nor 5-HT from the SN, whereas intranigral administration of the D1-receptor antagonist SCH-23390 HCl (10 microM) significantly increased both DA (to 214%) and 5-HT release (to 168%) from the SN. Co-perfusion of the D1-receptor agonist and antagonist did not change nigral DA nor 5-HT release compared to perfusion of the antagonist alone. The continuous intranigral perfusion of the D2-receptor agonist, (-)-quinpirole HCl (1 microM) significantly decreased both DA ad 5-HT release to 71% and 78%, respectively. These decreases were abolished when the D2-receptor antagonist S(-)-sulpiride (10 microM) and the D2-receptor agonist (-)-quinpirole HCl (1 microM) were co-perfused. In contrast, the intranigral perfusion of the DA precursor, L-DOPA (5 microM; 1 h), significantly increased nigral and striatal 5-HT release to 202% and 155%, respectively. This enhanced nigral 5-HT release might not be receptor-mediated. The results of the present study suggest a D1 and D2 regulation of nigral 5-HT release, either directly mediated by DA receptors on nigral 5-HT terminals or indirectly by nigral GABA, Glu or Asp. Alternatively, the observed DA-5HT-interaction in the SN might not reflect a local interaction but might involve an interaction at the level of the serotonin cell body region, the dorsal raphe nuclei (DRN).

Animals↗
PubMed1998

5-HT4 receptor involvement in the serotonin-enhanced dopamine efflux from the substantia nigra of the freely moving rat: a microdialysis study.

The functional regulation by serotonin (5-HT) receptors of the 5-HT-enhanced dopamine (DA) release from the rat substantia nigra (SN) was investigated using in vivo microdialysis. Exogenously administered or extracellularly enhanced 5-HT (by means of intranigral citalopram perfusion) (both 1 microM for 1 h) significantly increased nigral DA efflux to 165% and 145%, respectively. Intranigral administration of pindolol (10 microM, 3 h), a 5-HT1A/1B receptor antagonist which is clinically used in order to block 5-HT1A/1B autoreceptors, did not affect DA levels but significantly increased nigral 5-HT levels to 135%. Co-perfusion of this antagonist with 5-HT (1 microM, 1 h) did not abolish the 5-HT-induced DA release from the SN as DA was increased to 166%. Local application of the 5-HT1A/1B receptor agonist, CP 93129 (1 microM, 1 h), increased DA release from the SN to 4770% whereas 5-HT release was significantly decreased to 75%. Co-perfusion of the 5-HT1A/1B receptor antagonist, pindolol, with this agonist only partly abolished the CP 93129-induced DA release whereas the CP 93129-induced decrease in nigral 5-HT release was completely abolished. Administration of the 5-HT2A/2C receptor antagonist, ketanserin (50 microM, 3 h), significantly increased DA to 143% and 5-HT release to 363%. Co-perfusion of this antagonist with 5-HT still caused an increase in nigral DA release to 214%. Intranigral perfusion of the 5-HT4 receptor antagonist, RS 39604 (10 microM, 3 h), did not affect DA levels but significantly decreased nigral 5-HT levels to 74%. Co-perfusion of this antagonist with 5-HT was able to prevent the 5-HT-enhanced DA efflux from the SN. From this study it can be concluded that the 5-HT-enhanced (and possibly the citalopram-induced) nigral DA release is 5-HT4 receptor mediated.

Animals↗
PubMed1998

Biotransformation of L-DOPA to dopamine in the substantia nigra of freely moving rats: effect of dopamine receptor agonists and antagonists.

We investigated the effects of continuous intranigral perfusion of dopamine D1 and D2 receptor agonists and antagonists on the biotransformation of locally applied L-DOPA to dopamine in the substantia nigra of freely moving rats by means of in vivo microdialysis. The "dual-probe" mode was used to monitor simultaneously changes in extracellular dopamine levels in the substantia nigra and the ipsilateral striatum. Intranigral perfusion of 10 microM L-DOPA for 20 min induced a significant 180-fold increase in extracellular nigral dopamine level. No effect of the intranigral L-DOPA administration was observed on dopamine levels in the ipsilateral striatum, suggesting a tight control of extracellular dopamine in the striatum after enhanced nigral dopamine levels. Continuous nigral infusion with the D1 receptor agonist CY 208243 (10 microM) and with the D2 receptor agonist quinpirole at 10 microM (a nonselective concentration) attenuated the L-DOPA-induced increase in dopamine in the substantia nigra by 85 and 75%, respectively. However, perfusion of the substantia nigra with a lower concentration of quinpirole (1 microM) and the D1 antagonist SCH 23390 (10 microM) did not affect the nigral L-DOPA biotransformation. The D2 antagonist (-)-sulpiride (10 microM) also attenuated the L-DOPA-induced dopamine release in the substantia nigra to approximately 10% of that of the control experiments. We confirm that there is an important biotransformation of L-DOPA to dopamine in the substantia nigra. The high concentrations of dopamine formed after L-DOPA administration may be the cause of dyskinesias or further oxidative stress in Parkinson's disease. Simultaneous administration of D1 receptor agonists with L-DOPA attenuates the biotransformation of L-DOPA to dopamine in the substantia nigra. The observed effects could occur via changes in nigral GABA release that in turn influence the firing rate of the nigral dopaminergic neurons.

Animals↗
PubMed1997

Characterization of the extracellular serotonin release in the substantia nigra of the freely moving rat using microdialysis.

The characteristics of the serotonin release were investigated in the substantia nigra (SN) of the freely moving rat using microdialysis. We also examined whether the delay between surgery and microdialysis experiments might influence these characteristics by implanting rats with a guide cannula 1 or 2 days prior to microdialysis experiments. In the first group, the tissue was not punctured until the microdialysis probe was inserted the evening before the experiment. In the second group, the nigral tissue was punctured with an extended obturator which was then replaced by a microdialysis probe the evening before the experiment. After administration of 60 mM K+ a more pronounced increase in serotonin was observed in the first group (260%) compared to the second group (159%). Calcium-free and tetrodotoxin (TTX, a sodium channel blocker) (1 microM) perfusion reduced extracellular serotonin to respectively 77% and 80% in the first group and 70% and 64% in the second group. These results suggest that vesicular release of nigral serotonin only occurs partially in this region and that minimizing the damage caused by implantation of the probe results only in 10% more vesicular release of serotonin. However, blockade of the serotonin reuptake carrier caused more TTX sensitivity of the serotonin release. Also, stimulation of the dorsal raphe by locally perfusing 60 mM K+ decreased serotonin in the SN, confirming the anatomical and functional link between both areas.

Animals↗
PubMed1997

Differential effects of restraint stress on hippocampal 5-HT metabolism and extracellular levels of 5-HT in streptozotocin-diabetic rats.

Streptozotocin (STZ)-elicited diabetes reduces central serotonin (5-hydroxytryptamine, 5-HT) synthesis/metabolism, but whether this reduction leads to decreased release of 5-HT has only scarcely been investigated. We have thus analysed the impact of STZ diabetes on hippocampal extracellular 5-HT levels both under basal conditions and during restraint stress, a procedure known to stimulate hippocampal 5-HT synthesis/metabolism and release. The pretreatment with STZ (3 weeks beforehand) and the 1 h restraint session respectively decreased and increased hippocampal 5-HT metabolism, as assessed by tissue analysis of 5-HT and 5-hydroxyindoleacetic acid. On the other hand, hippocampal microdialysis revealed no difference in basal levels of extracellular 5-HT levels in (conscious) vehicle- and STZ-pretreated rats, but a differential effect of restraint. Thus, extracellular 5-HT levels increased throughout restraint (maximal increase: 194%) in vehicle-, but not in STZ-pretreated rats. In the latter rat group, plasma corticosterone levels were, however, increased, thus indicating a significant aversiveness to stress. Lastly, because anxiety-related behaviours may be affected by hippocampal serotonergic systems, resting and restrained vehicle- and STZ-pretreated rats were compared (immediately after stress) in an elevated plus-maze of anxiety. Pretreatment with STZ reduced the percent number of open arm entries and the number of closed arm entries, indicating increased anxiety and reduced locomotor activity, respectively. Restraint tended to increase anxiety-related behaviours in all rats, but this trend never reached significance. Our results confirm that gross analyses of 5-HT metabolism do not yield information on 5-HT release, and suggest that the prevalence of diabetes among patients suffering affective disorders could be related to the lack of hippocampal serotonergic response to aversive stimuli.

Animals↗
PubMed1997

New antioxidant mixture for long term stability of serotonin, dopamine and their metabolites in automated microbore liquid chromatography with dual electrochemical detection.

An automated microbore liquid chromatographic assay with dual electrochemical detection is described for the determination of serotonin, dopamine and their metabolites, 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid and homovanillic acid. Due to the chemical instability of the compounds, the addition of an antioxidant is required for automated analysis over a long period of time (e.g., 20 h). Therefore, the time stability of these substances was tested with different antioxidants. The stability for serotonin and 5-hydroxyindoleacetic acid was poor in acidic medium containing Na2EDTA but could greatly be improved by the addition of L-cysteine and ascorbic acid. Using this assay, the neurotransmitters and their metabolites could easily be determined in microdialysates obtained from different rat brain areas.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Distribution of apomorphine enantiomers in plasma, brain tissue and striatal extracellular fluid.

Steady-state concentrations of apomorphine enantiomers were measured in the extracellular fluid collected from rat brain striatum by microdialysis. The free and total concentrations of both enantiomers were also measured in plasma as well as the total concentrations in different brain regions (striatum, cortex and cerebellum). We noticed no regional difference in the total concentrations of the two enantiomers. The extracellular concentrations were much lower, amounting to 8% for R(-)-apomorphine and 4% for S(+)-apomorphine, of the total brain tissue concentrations. The microdialysis samples contained 12 times more (R(-)-apomorphine and 5 times more S(+)-apomorphine than the free apomorphine measured in plasma. The extracellular concentrations of R(-)-apomorphine (129 +/- 20 pmol/ml) were significantly higher (P = 0.001, n = 6), than those of S(+)-apomorphine (70 +/- 10 pmol/ml). These results indicate that both enantiomers of apomorphine concentrate equally in brain cells, and that a stereoselective uptake system could operate for R(-)-apomorphine at the blood-brain barrier level.

Animals↗
PubMed1997

Hippocampal and cerebellar extracellular amino acids during pilocarpine-induced seizures in freely moving rats.

Limbic seizures were provoked in freely moving rats by intrahippocampal administration of the muscarinic receptor agonist pilocarpine via a microdialysis probe (10 mM for 40 min at 2 microliters/min). Changes in extracellular hippocampal and cerebellar glutamate, aspartate and gamma-aminobutyric acid (GABA) levels were monitored during and after pilocarpine administration. Effects of systemic or local administration of anticonvulsants on the seizures and concomitant changes in amino-acid concentrations, were investigated. Pilocarpine-induced seizures were completely abolished after intraperitoneal premedication for 7 days with phenobarbital (15 mg/kg per day) and after intrahippocampal administration of 10 mM phenobarbital and 1 mM carbamazepine (180 min at 2 microliters/min). Rats premedicated with carbamazepine (5 mg/kg per day) still developed seizures. The changes in extracellular hippocampal amino-acid levels suggest that glutamate, aspartate and GABA are not involved in seizure onset, but may play a role in seizure maintenance and/or spread in the pilocarpine animal model of epilepsy. The increases in extracellular amino acids in ipsi- and contralateral cerebellum following limbic seizures provoked in the hippocampus, probably play a role in the 'reversed' diaschisis phenomenon.

Amino Acids↗
PubMed1997

Biotransformation of locally applied precursors of dopamine, serotonin and noradrenaline in striatum and hippocampus: a microdialysis study.

In vivo microdialysis in freely moving rats was used to study the biotransformation, consisting primarily of decarboxylation by aromatic amino acid decarboxylase (AAAD), of the precursors L-3,4-dihydroxyphenylalanine (L-DOPA), L-5-hydroxytryptophan (L-5HTP), and L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) on extracellular levels of dopamine (DA), serotonin (5HT) and noradrenaline (NA), respectively. The precursors were administered locally through the microdialysis probe into the striatum and into the hippocampus. The different transmitter systems were compared with respect to the ability of the precursors to elevate extracellular levels of their associated transmitter. The basal extracellular concentrations of NA and DA were found to be tetrodotoxin (TTX, a blocker of fast sodium channels) sensitive in striatum and hippocampus, indicating the neuronal origin of the measured transmitters. The extracellular concentrations of 5HT (in hippocampus) were only 60% TTX-sensitive. L-DOPA and L-5HTP showed to be effective precursors of DA and 5HT, respectively, although their formation profile was quite different. The L-DOPA-induced increase in extracellular DA was large and short-lasting, while the L-5HTP-induced increase in 5HT was slower and less pronounced. The relative increase in extracellular DA or 5HT was more pronounced in the brain region where their baseline values were lower, but the absolute amount of transmitter formed from their precursor was similar in both brain regions. L-threo-DOPS was a poor precursor for NA and also failed to influence extracellular DA in striatum, questioning its use in the treatment of freezing gait in late stages of Parkinson's disease.

5-Hydroxytryptophan↗
PubMed1997

NMDA receptor-mediated pilocarpine-induced seizures: characterization in freely moving rats by microdialysis.

1. Pilocarpine administration has been used as an animal model for temporal lobe epilepsy since it produces several morphological and synaptic features in common with human complex partial seizures. Little is known about changes in extracellular neurotransmitter concentrations during the seizures provoked by pilocarpine, a non-selective muscarinic agonist. 2. Focally evoked pilocarpine-induced seizures in freely moving rats were provoked by intrahippocampal pilocarpine (10 mM for 40 min at a flow rate of 2 microl min(-1)) administration via a microdialysis probe. Concomitant changes in extracellular hippocampal glutamate, gamma-aminobutyric acid (GABA) and dopamine levels were monitored and simultaneous electrocorticography was performed. The animal model was characterized by intrahippocampal perfusion with the muscarinic receptor antagonist atropine (20 mM), the sodium channel blocker tetrodotoxin (1 microM) and the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (dizocilpine maleate, 100 microM). The effectiveness of locally (600 microM) or systemically (10 mg kg(-1) day(-1)) applied lamotrigine against the pilocarpine-induced convulsions was evaluated. 3. Pilocarpine initially decreased extracellular hippocampal glutamate and GABA levels. During the subsequent pilocarpine-induced limbic convulsions extracellular glutamate, GABA and dopamine concentrations in hippocampus were significantly increased. Atropine blocked all changes in extracellular transmitter levels during and after co-administration of pilocarpine. All pilocarpine-induced increases were completely prevented by simultaneous tetrodotoxin perfusion. Intrahippocampal administration of MK-801 and lamotrigine resulted in an elevation of hippocampal dopamine levels and protected the rats from the pilocarpine-induced seizures. Pilocarpine-induced convulsions developed in the rats which received lamotrigine perorally. 4. Pilocarpine-induced seizures are initiated via muscarinic receptors and further mediated via NMDA receptors. Sustained increases in extracellular glutamate levels after pilocarpine perfusion are related to the limbic seizures. These are arguments in favour of earlier described NMDA receptor-mediated excitotoxicity. Hippocampal dopamine release may be functionally important in epileptogenesis and may participate in the anticonvulsant effects of MK-801 and lamotrigine. The pilocarpine-stimulated hippocampal GABA, glutamate and dopamine levels reflect neuronal vesicular release.

Animals↗
PubMed1997

Endurance training effects on neurotransmitter release in rat striatum: an in vivo microdialysis study.

In the present study we use the in vivo microdialysis sampling technique to register extracellular levels of neurotransmitters in the striatum of trained and untrained rats. We further evaluate the influence of 1 h of exercise on the striatal release of dopamine (DA), noradrenaline (NA), glutamate (GLU) and gamma-aminobutyric acid (GABA) in trained and untrained rats. Male Wistars were randomly assigned to a training or control group. The exercise training consisted of running on a treadmill for 6 weeks, 5 days week-1, with running time and speed gradually increased from 30 min at 19 m min-1 during the first week to 80 min at 26 m min-1 during the final training week. The animals of the control group were placed on the treadmill twice a week, and received a total of four 'adaptation sessions', in which they exercised 15-45 min at 26 m min-1. Brain dialysates were analysed with microbore liquid chromatography (LC), with electrochemical detection (monoamines and GABA) and fluorescence detection (GLU). Soleus citrate synthase and basal striatal concentrations of DA, NA and GLU were significantly different between the trained and control animals. Sixty minutes of exercise significantly increased extracellular DA, NA and GLU levels in both groups, but there was no statistically significant difference in the exercise-induced increase between trained and control animals. There was no statistical difference in basal or exercise-induced GABA levels between trained and control animals. The results indicate that exercise training appears to result in diminished basal activity of striatal neurotransmitters, while maintaining the necessary sensitivity for responses to acute exercise.

Animals↗
PubMed1997

Muscarinic modulation of striatal dopamine, glutamate, and GABA release, as measured with in vivo microdialysis.

Intrastriatal microdialysis was used to administer muscarinic drugs in freely moving rats for 40 min at a flow rate of 2 microl/min. Administration of the nonselective agonist pilocarpine at 10 mM increased striatal dopamine release and decreased extracellular GABA and glutamate overflow. Perfusion with the muscarinic M2 antagonist methoctramine at 75 microM increased extracellular dopamine and glutamate concentrations but exerted no changes on extracellular GABA levels. Intrastriatal administration of the M1 antagonist pirenzepine at 0.05 microM decreased extracellular dopamine overflow. Application of pirenzepine (0.05 and 5 microM) exerted no effects on the measured GABA or glutamate levels. There are thus important differences in applied doses of muscarinic drugs needed to obtain modulatory effects. High doses of agonists are probably needed to superimpose on the background of tonic influences of striatal acetylcholine, whereas antagonists can block the receptors in small doses. We further suggest that M1 receptors might tonically facilitate striatal dopamine release, that M2 receptors might tonically inhibit striatal glutamate efflux, and that acetylcholine does not exert tonic effects on striatal GABA release. The link with the pilocarpine animal model for temporal lobe epilepsy will be discussed.

Animals↗