Biomedical subjects

W Balduini

Publications and source records attributed to W Balduini.

At least 37 records · Page 2Linked to original sources

PubMed1992

Cholinergic hyperinnervation in the cerebral cortex of microencephalic rats does not result in muscarinic receptor down-regulation or in alteration of receptor-stimulated phosphoinositide metabolism.

Administration of methylazoxymethanol (MAM; 25 mg/kg) to pregnant rats at gestational day 15 (GD 15) induces a marked reduction of telencephalic areas of the offspring brain. Previous neurochemical studies demonstrated a marked cholinergic hyperinnervation in the cerebral cortex of microencephalic rats. In this study we have evaluated whether this cholinergic hyperinnervation could result in altered functionality of muscarinic receptors. Acetylcholinesterase activity (AChE) was increased by 69% in the cerebral cortex of MAM treated rats, confirming a relative hyperinnervation, whereas in the hippocampus and striatum no significant changes were observed. Despite the marked hyperinnervation, in the cerebral cortex of microencephalic rats neither muscarinic receptor-stimulated phosphoinositide metabolism nor muscarinic receptor density were altered. No differences in receptor density were also observed in the hippocampus and striatum. Chronic diisopropylfluorophosphate (DFP) administration induced a marked decrease of AChE activity and down-regulation of muscarinic receptors whereas atropine administration resulted in receptor up-regulation in cerebral cortex, striatum and hippocampus of both control and MAM rats. The results confirm a relative cholinergic hyperinnervation in the cerebral cortex of microencephalic rats and demonstrate that the regulation of muscarinic receptor-stimulated phosphoinositide metabolism and muscarinic receptor plasticity is not modified in a condition of increased cholinergic presynaptic terminals.

Abnormalities, Drug-Induced↗

PubMed1992

Structure-activity relationships of N-n-propyl-2-(4-fluoro-3-hydroxyphenyl)ethylamine derivatives as dopamine receptor ligands.

A series of N-n-propyl-2-(4-fluoro-3-hydroxyphenyl)ethylamine derivatives obtained by introducing on nitrogen atom a 2-phenylethyl moiety (with aromatic nucleus substituted at 3 or 4 position with fluorine, chlorine or hydroxy and methyl groups), as well as a 2-cyclohexylethyl or 3-phenylpropyl groups were synthesized. These substituents can interact with the D2 accessory binding site pi 3. The affinities of new compounds for D1 and D2 subtypes of dopamine (DA) receptor were measured in a test involving displacement of [3H]SCH 23390 and [3H]spiperone, respectively, from homogenates of rat striatum. The new derivatives are selective for D2 sites, and are more potent than the parent compound N-n-propyl-N-(2-phenylethyl)-2-(4-fluoro-3-hydroxyphenyl)ethylamine 2a. The N-n-propyl-N-[2-(4-hydroxyphenyl)ethyl]-2-(4-fluoro-3-hydroxyphenyl) ethylamine (11f) is the most potent and selective member in the series. Other derivatives are less effective but are as potent as the D2 agonist RU 24213. The results indicate that the pi 3 site is a rather large lipophilic pocket which can accommodate not only aromatic nuclei, but also the cyclohexyl group.

Animals↗

PubMed1991

Regional development of carbachol-, glutamate-, norepinephrine-, and serotonin-stimulated phosphoinositide metabolism in rat brain.

Phosphoinositide metabolism stimulated by activation of cholinergic muscarinic, glutamatergic, alpha-adrenergic and serotoninergic receptors was measured in brain regions of the developing rats. Accumulation of [3H]inositol phosphates ([3H]InsPs) in [3H]inositol-prelabeled slices from cerebral cortex, hippocampus, brainstem and cerebellum was measured as an index of phosphoinositide metabolism. Large age-, neurotransmitter receptor-, and brain region-dependent differences were found. Carbachol-stimulated [3H]InsPs accumulation peaked on postnatal day 7 in cerebral cortex and hippocampus while in cerebellum and brainstem the effect of muscarinic stimulation was maximal at birth and then declined to adulthood. The effect of glutamate also showed a peak on day 7 in hippocampus and brainstem and a developmentally related decrease in cerebral cortex. In the cerebellum, on the other hand, the response to glutamate remained sustained through adulthood. Stimulation of phosphoinositide metabolism by norepinephrine increased with age in hippocampus and cerebral cortex, but decreased in the cerebellum, while the effect of serotonin did not change significantly with age except in cerebellum. These changes in receptor-stimulated phosphoinositide metabolism do not parallel, for the most part, the ontogeny of receptor recognition sites. Activation of the phosphoinositide metabolism pathway leads to an increase in intracellular calcium levels and to stimulation of protein kinase C, which are believed to play significant roles in cellular proliferation and differentiation. Thus, the differential ability of neurotransmitters to stimulate phosphoinositide hydrolysis might play a role in the development of brain regions.

Acetylcholine↗

PubMed1991

Time-, concentration-, and age-dependent inhibition of muscarinic receptor-stimulated phosphoinositide metabolism by ethanol in the developing rat brain.

We have previously reported that administration of ethanol (EtOH; 4 g/Kg/day) to rats from postnatal day 4 to day 10 causes microencephaly and decreases muscarinic receptor-stimulated inositol metabolism on days 7 and 10. An identical exposure to EtOH of adult rats, which resulted in similar blood EtOH concentrations, did not have any effect on the same system. Initial in vitro studies have shown the presence of a differential sensitivity to EtOH of the phosphoinositide system coupled to muscarinic receptors during development. In the present study we have expanded these findings by investigating the concentration-, time-, and age-dependent effects of EtOH on accumulation of [3H]inositol phosphates ([3H]InsPs) in brain slices. EtOH caused a dose-dependent inhibition of carbachol-stimulated phosphoinositide metabolism in cerebral cortex slices from 7 day-old rats. When the time of incubation with EtOH was increased to 90 minutes, concentrations as low as 50 mM, which are reached following in vivo administration of EtOH, significantly inhibited the muscarinic response. The effect of EtOH was rather specific for the muscarinic receptors, since, even with longer incubation times, the accumulation of [3H]InsPs induced by norepinephrine or serotonin was inhibited only at concentrations of 150-500 mM. The effect of EtOH was more pronounced in cerebral cortex, hippocampus and cerebellum, and less in the brainstem. The potency of EtOH in inhibiting carbachol-stimulated phosphoinositide metabolism was also dependent on the age of the animals. Its effect was maximal in the 7-day-old rat and less pronounced in younger and older animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1991

Treatment with methylazoxymethanol at different gestational days: two-way shuttle box avoidance and residential maze activity in rat offspring.

Pregnant rats were injected with a single dose of methylazoxymethanol (MAM, 25 mg/kg) on gestational days 14, 15, 16, 17, 18 or 19 which resulted in various degrees of microencephaly. Offspring were tested on a two-way shuttle box avoidance and residential maze activity at 60-90 days of age. Rats treated on gestational day 19 (GD19) were severely impaired in the acquisition of the two-way shuttle box task whereas the other groups did not show any significant difference from controls. Spontaneous activity measured for 23 hr in the residential maze was altered as total, time-course and pattern depending on the time of MAM administration: treatment on GD14 prolonged exploratory behavior, treatment on GD15 and GD16 increased nocturnal activity, treatment on GD16 and GD17 induced changes in locomotion patterns and treatment on GD18 and GD19 decreased total activity. These findings indicate that treatment with MAM results in selective deficits in the acquisition of a shuttle box avoidance and alterations of locomotion patterns in the offspring which are dependent on the time of administration.

Alkylating Agents↗

PubMed1991

Interaction of short chain aliphatic alcohols with muscarinic receptor-stimulated phosphoinositide metabolism in cerebral cortex from neonatal and adult rats.

Muscarinic receptor-stimulated phosphoinositide metabolism has been recently suggested as a possible target for the neurotoxic effects of ethanol during brain development. Since two other alcohols, tertiary butanol and n-propanol, have been shown to cause microencephaly in the rat when administered during the brain growth spurt, in the present study we investigated the in vitro effects of five short chain aliphatic alcohols on muscarinic receptor-stimulated phosphoinositide metabolism in cerebral cortical slices from 7 day-old rats. In neonatal animals all alcohols tested inhibited carbachol (1 mM)-stimulated [3H]inositol phosphates accumulation in a dose- and time-dependent manner. The order of potency was t-butanol greater than n-propanol greater than or equal to iso-propanol greater than ethanol greater than methanol. After 90 min of incubation, ethanol, n-propanol and t-butanol caused a significant inhibition of muscarinic receptor-stimulated inositol metabolism at doses as low as 15 - 50 mM, comparable to the blood concentrations reached after in vivo administration of doses able to induce developmental neurotoxicity. The inhibitory effect of ethanol was additive to that of iso-propanol or t-butanol. Differently from these effects in 7 day-old rats, in cortical slices from adult animals methanol and ethanol had no effect on carbachol-stimulated phosphoinositide metabolism, while the two propanol isomers and t-butanol were less effective than in neonatal animals. These results suggest that muscarinic receptor-coupled phosphoinositide metabolism might be a common neurochemical target for the developmental neurotoxicity of short chain aliphatic alcohols.

Alcohols↗

PubMed1991

Treatment with methylazoxymethanol at different gestational days: physical, reflex development and spontaneous activity in the offspring.

Pregnant rats were injected with a single dose of methylazoxymethanol (MAM, 25 mg/kg) on gestational day 14, 15, 16, 17, 18 or 19 and offspring were tested for their physical development, reflex development and spontaneous activity. MAM treatment did not affect gestational and litter parameters at any of the time of administration studied. Treatment at gestational day 14 (GD14) had the most severe effect on functional neurodevelopment until weaning: righting reflex at surface, chimney test, horizontal wire test resulted altered. Administration at GD15, 16, 18, 19 did not affect the performance in these tests. Offspring treated at GD17 showed a delayed eye opening and an impaired performance in the horizontal wire test. When tested at 50 days of age on the rotarod, all the treated groups performed worse than controls with the exception of GD19 treated offspring. Administration at GD14 and GD15 resulted in increased spontaneous activity of the offspring at 21 days but not at 60 days of age. Different degrees of microencephaly were observed for all treated groups. The results indicate that alterations of physical and behavioral development induced by MAM treatment are dependent on the time of MAM administration, and specific behavioral tests are able to detect different abnormalities and differentiate among treatment groups. Some alterations observed in MAM rats undergo to adaptive changes during maturation of the CNS.

Animals↗

PubMed1990

Developmental neurotoxicity of ethanol: in vitro inhibition of muscarinic receptor-stimulated phosphoinositide metabolism in brain from neonatal but not adult rats.

The in vitro effects of ethanol (EtOH) on muscarinic receptor-stimulated phosphoinositide metabolism were measured in cerebral cortex slices of adult and 7-day-old rats. EtOH (500 mM) caused a significant decrease (32-43%) of maximal accumulation of [3H]inositol phosphates (InsPs) induced by carbachol, and a 2-fold increase in its EC50 in 7-day-old rats, but had no effect in adult rats. The effect of EtOH on [3H]InsPs accumulation in neonatal rats was significant at a concentration as low as 150 mM. The inhibitory effect of EtOH was maximal in cerebral cortex and hippocampus and lower in cerebellum, while no effect was observed in the brainstem. While carbachol- and acetylcholine-stimulated phosphoinositide metabolism were inhibited by EtOH, EtOH had no effect on norepinephrine-, histamine-, and serotonin-stimulated phosphoinositide hydrolysis. These results are qualitatively and quantitively similar to those previously found following in vivo administration of EtOH to developing and to adult rats, suggesting that the muscarinic receptor-stimulated phosphoinositide metabolism might represent a target for EtOH-induced developmental neurotoxicity.

Aging↗

PubMed1990

Characterization of ouabain-induced phosphoinositide hydrolysis in brain slices of the neonatal rat.

The effect of the Na/K-ATPase inhibitor ouabain on phosphoinositide (Ptdlns) hydrolysis was studied in rat brain cortical slices. Ouabain induced a dose-dependent accumulation of inositol phosphates (InsPs) which was much higher in neonatal rats (1570 +/- 40% of basal) than in adult animals (287 +/- 18% of basal). For this reason, all experiments were conducted with 7 day-old rats. Strophantidin caused a similar stimulation of Ptdlns hydrolysis, although it was less potent than ouabain. The order of potency for ouabain-stimulated InsPs accumulation in brain areas was hippocampus greater than cortex greater than brainstem greater than cerebellum. The effect of ouabain was not blocked by antagonists for the muscarinic, alpha1 -adrenergic and glutamate receptors. Also ineffective were the K+ channel blockers 4-aminopyridine and tetraethylammonium, the sodium channel blocker tetrodotoxin, and the calcium channel blocker verapamil, whereas the Na/Ca exchanger blocker amiloride partially antagonized the effect of ouabain. The accumulation of InsPs induced by ouabain was additive to that of carbachol and norepinephrine, as well as to that induced by high K+ and veratrine, but not to that of glutamate. Removal of Na+ ions from the incubation buffer completely prevented the accumulation of InsPs induced by ouabain. The effect of ouabain was also dependent upon extracellular calcium and was under negative feedback control of protein kinase C. Despite the higher effect of ouabain on Ptdlns hydrolysis of immature rats, the density of [3H]ouabain binding sites, as well as the activity of Na/K-ATPase were higher in adult animals. Furthermore, a poor correlation was found between ouabain-stimulated Ptdlns hydrolysis and [3H]ouabain binding in brain regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1990

Potassium ions potentiate the muscarinic receptor-stimulated phosphoinositide metabolism in cerebral cortex slices: a comparison of neonatal and adult rats.

Activation of cholinergic muscarinic receptors results in an increased turnover of membrane inositol phospholipids. In rat cerebral cortex slices, carbachol- and acetylcholine-induced inositol phosphates ([3H]InsPs) accumulation is maximal in 7 day-old rats and lowest in adults, while the density of muscarinic binding sites increases gradually with age, suggesting the presence of a more effective receptor-effector coupling during neonatal life. In the process of investigating the nature of such differential stimulation, we have studied the effects of potassium ions on muscarinic receptor-stimulated phosphoinositide metabolism during development. Increasing the concentration of K+ from 6 to 12 mM potentiated the stimulating effect of carbachol by 80-100% in adult animals, as previously shown, but only 10-20% in 7 day-old animals, without altering its EC50 values. The differential potentiation by K+ at these two ages was specific for muscarinic receptors, since norepinephrine-stimulated accumulation was potentiated only 18% and 12% in adult and 7 day-old rats, respectively. Two other monovalent cations, rubidium and cesium, had the same effect as K+ on carbachol-stimulated [3H]-InsPs accumulation. The effect of K+ was not antagonized by the K+ channel blocker 4-aminopyridine, but was antagonized by tetraethylammonium (TEA). TEA, however, also interacted with muscarinic binding sites. Omission of calcium from the incubation medium did not influence the potentiating effect of K+ during development was inversely proportional to the stimulation of phosphoinositide metabolism induced by carbachol. These results suggest that the mechanism responsible for the potentiating effect of K+ in adult rats might be already operating in neonatal animals.

Aging↗

PubMed1990

Synthesis and dopamine receptor affinities of 2-(4-fluoro-3- hydroxyphenyl)ethylamine and N-substituted derivatives.

The synthesis of 2-(4-fluoro-3-hydroxyphenyl)ethylamine (26) and of some N,N-dialkyl derivatives (27-30) starting from 4-fluoro-3-hydroxytoluene and their in vitro binding affinities for dopamine (DA) receptor are reported. The amine 26 can be regarded as a molecular modification of DA in which the para hydroxyl group is replaced by fluorine. The new compounds 26-30 were evaluated for their affinity at D-1 and D-2 DA receptor subtypes by displacement of [3H]SCH 23390 (D-1 selective) and [3H]spiperone (D-2 selective). The amine 26 had about 2-fold less affinity for D-1 and D-2 binding sites than DA. The substitution of the amino group with ethyl, n-propyl, and 2-phenylethyl groups decreased the affinity for D-1 binding sites but greatly enhanced the effectiveness on D-2 binding sites. The N-ethyl- (28) and N-n-propyl-N-(2-phenylethyl)-2-(4-fluoro-3- hydroxyphenyl)ethylamine (30) were the most potent members of the series with high selectivity for D-2 binding sites. A similar effect was observed with isomeric N-n-propyl-N-(2-phenylethyl)-2-(3-fluoro-4-hydroxyphenyl)ethylamine (31) which was approximately 65 times more selective for D-2 sites vs D-1 sites. The introduction of a 2-phenylethyl group on the nitrogen atom induce the highest effect, perhaps as a consequence of an increased liposolubility or of binding to a complementary lipophilic site on the receptor.

Animals↗

PubMed1990

Characterization of cholinergic muscarinic receptor-stimulated phosphoinositide metabolism in brain from immature rats.

Hydrolysis of phosphoinositides elicited by stimulation of cholinergic muscarinic receptors has been studied in brain from neonatal (7-day-old) rats in order to determine: 1) whether the neonatal rat could provide a good model system to study this signal-transduction pathway; and 2) whether potential differences with adult nerve tissue would explain the differential, age-related effects of cholinergic agonists. Accumulation of [3H] inositol phosphates in [3H]inositol prelabeled slices from neonatal and adult rats was measured as an index of phosphoinositide metabolism. Full (acetylcholine, methacholine, carbachol) and partial (oxotremorine, bethanechol) agonists had qualitatively similar, albeit quantitatively different, effects in neonatal and adult rats. Atropine and pirenzepine effectively blocked the carbachol-induced response with inhibition constants of 1.2 and 20.7 nM, respectively. In all brain areas, response to all agonists was higher in neonatal than adult rats, and in hippocampus and cerebral cortex the response was higher than in cerebellum or brainstem. The relative intrinsic activity of partial agonists was higher in the latter two areas (0.6-0.7) than in the former two (0.3-0.4). Carbachol-stimulated phosphoinositide metabolism in brain areas correlated well with the binding of [3H]QNB (r2 = 0.627) and, particularly, with [3H]pirenzepine (r2 = 0.911). In cerebral cortex the effect of carbachol was additive to that of norepinephrine and glutamate. The presence of calcium (250-500 microM) was necessary for maximal response to carbachol to be elicited; the EC50 value for Ca2+ was 65.4 microM. Addition of EDTA completely abolished the response. Removal of sodium ions from the incubation medium reduced the response to carbachol by 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1989

Effects of ethanol on muscarinic receptor-stimulated phosphoinositide metabolism during brain development.

The pattern of muscarinic receptor-stimulated inositol metabolism during postnatal development has a striking resemblance with the curve of rat brain growth spurt. Therefore, the enhanced hydrolysis of membrane inositol lipids by cholinergic agonists during this period may have a relevant role in cell proliferation and differentiation. In this study we have investigated whether exposure to EtOH to rat pups during the brain growth spurt, known to cause a permanent microencephaly, would alter muscarinic receptor-stimulated inositol metabolism in cerebral cortex. Female Long-Evans rats were administered 4 g/kg of EtOH, in two doses of 2 g/kg, by gastric intubation from postnatal day 4 to day 10. This treatment did not have any effect on the pups' body weight as compared to an equally handled, sucrose-fed group of animals. Blood EtOH concentration in the pups during exposure ranged between 237 and 283 mg/dl. Muscarinic receptor-stimulated inositol metabolism was measured in cerebral cortex slices of control and EtOH-treated rats at days 4, 7, 10, 12, 20 and 45 of age. Carbachol-induced accumulation of [3H] inositol phosphates was reduced significantly in EtOH-exposed animals on day 7 and 10, but not at other ages. This decrease was not due to an alteration of muscarinic receptor density or affinity. Exposure to EtOH had no effect on phosphoinositide metabolism stimulated by norepinephrine, serotonin or histamine in cerebral cortex, whereas the effect of glutamate was increased. Similar results were observed in the hippocampus. An identical treatment with EtOH in adult rats did not cause alteration in any of the biochemical parameters of the cholinergic system measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Synthesis and dopamine receptors binding affinity of 2-(3-fluoro-4-hydroxyphenyl)ethylamine and its N-alkyl derivatives.

The 2-(3-fluoro-4-hydroxyphenyl)ethylamine and its N,N-dialkyl derivatives were synthesized. The affinity of new compounds for dopamine binding sites was measured in a test involving displacement of [3H]SCH 23390 (D-1 selective) and [3H]spiperone (D-2 selective) from homogenized rat striatal tissue. No compound proved effective in displacing [3H]SCH 23390. Two derivatives are selective displacers of [3H]spiperone.

Animals↗

PubMed1987

Developmental changes in muscarinic receptor-stimulated phosphoinositide metabolism in rat brain.

Muscarinic receptor-stimulated phosphoinositide hydrolysis was investigated in rat brain during ontogeny by measuring the accumulation of [3H]inositol phosphates ([3H]InsPs) in cerebral cortex slices at various ages. Experiments with carbachol and acetylcholine showed that [3H]InsPs accumulation was maximal in 7-day-old rats (1477 +/- 98% of basal) and lowest in adult (75 days) rats (428 +/- 24% of basal). No differences were found in the EC50 values for both cholinergic agonists. This effect appeared to be mediated by the M1-muscarinic receptor subtype as it was blocked by pirenzepine with Ki = 29.1 +/- 7.1 nM (adults) and 87.9 +/- 18.2 nM (7-day-old rats). Incorporation of [3H]inositol into phospholipid decreased from day 3 to adulthood; however, when data of [3H]InsPs release were corrected for the incorporation at a given age, the highest stimulation by cholinergic agonists was still observed in 7-day-old rats. Among the other neurotransmitters tested (norepinephrine, histamine and serotonin), all known to stimulate phosphoinositide metabolism, none had the same developmental profile of [3H]InsPs accumulation as cholinergic agonists. In contrast to carbachol- and acetylcholine-stimulated phosphoinositide hydrolysis, the density of muscarinic binding sites, measured by [3H]quinuclidinyl benzilate binding, increased from day 3 to day 75. Acetylcholinesterase activity also increased during development. The dissociation of receptor binding sites from receptor-stimulated phosphoinositide metabolism suggests the presence of a more effective receptor-effector coupling at specific times of neonatal development, particularly 1 week. Furthermore, the fact that maximal stimulation of phosphoinositide hydrolysis coincides with the period of brain growth spurt in the rats suggests that this system in the cerebral cortex might be involved in the processes of cell division and differentiation.

Acetylcholine↗

PubMed1987

Interaction of some 2-hydroxybenzylpiperidines with dopamine receptors.

Some N-alkyl derivatives of 2-(3-hydroxybenzyl)piperidine and of 2-(3,4-dihydroxybezyl)piperidine were synthesized and evaluated pharmacologically in vitro by competition with [3H]spiperone for binding to a homogenized rat striatal tissue, and for ability to stimulate adenylate cyclase. The N-methyl-2-(3,4-dihydroxybenzyl)piperidine shows a fairly good affinity for the D-2 dopamine receptor. The N-alkyl 2-(3,4-dihydroxybenzyl)piperidines produce a faible stimulation of adenylate cyclase activity.

Adenylyl Cyclase Inhibitors↗

PubMed1986

1,3 dideazaadenosine is a mitogen for cultured mammalian cells.

The effect of 1,3-dideazaadenosine (c1,3Ado) on DNA synthesis and rate of proliferation was measured in various mammalian cell lines. Vero, HeLa, CHO and SV40 3T3 cells displayed equal sensitivity to the stimulatory effect of the drug. Further experiments performed with Vero cells have indicated that the action of c1,3Ado was prompt, cell density dependent and did not result from an increased cell membrane permeability to exogenous labelled thymidine. c1,3Ado increased cell proliferation in 6 different normal or transformed cell lines. This data indicates that c1,3Ado displays mitogenic properties in cultured mammalian cells.

Animals↗

PubMed1986

Microencephalic rats as a model for cognitive disorders.

The administration of the antimitotic compound methylazoxymethanol (MAM) to gestating rats induces a dose-dependent atrophy of specific brain areas in the offspring. This specificity is strictly dependent upon the time of MAM administration. When given at day 15 of gestation only the cortex, hippocampus, and striatum are affected, whereas when given to rat pups at postnatal day 1, the atrophy is apparent only in the cerebellum. The microencephalic offspring of dams treated at day 15 of gestation develop normally to adulthood, without manifest signs of this profound telencephalic contraction. Behavioral abnormalities are observable when subjecting these animals to tests that involve learning. The deficit in associative behavior might have its anatomical and neurochemical counterpart in the disruption of the neuronal circuitry in the neocortex, where about 50% of interneurons are absent in layers II-IV after a dose of MAM of 25 mg/kg. Loss of intrinsic neurons occurs also in the striatum, as revealed by neurochemical and pharmacological analysis. Indeed, MAM rats show a reduced dopamine-dependent adenylate cyclase activity and a reduced motor stimulation in response to dopaminergic stimulants. MAM rats are therefore an interesting animal model of chronic brain damage induced transplacentally, which could serve for studying adaptive mechanisms of the CNS to this damage and its pharmacological manipulation.

Animals↗