Corpora Striata Research Articles

Physical exercise prevents motor disorders and striatal oxidative imbalance after cerebral ischemia-reperfusion.

Stroke is the third most common cause of death worldwide, and most stroke survivors present some functional impairment. We assessed the striatal oxidative balance and motor alterations resulting from stroke in a rat model to investigate the neuroprotective role of physical exercise. Forty male Wistar rats were assigned to 4 groups: a) control, b) ischemia, c) physical exercise, and d) physical exercise and ischemia. Physical exercise was conducted using a treadmill for 8 weeks. Ischemia-reperfusion surgery involved transient bilateral occlusion of the common carotid arteries for 30 min. Neuromotor performance (open-field and rotarod performance tests) and pain sensitivity were evaluated beginning at 24 h after the surgery. Rats were euthanized and the corpora striata was removed for assay of reactive oxygen species, lipoperoxidation activity, and antioxidant markers. Ischemia-reperfusion caused changes in motor activity. The ischemia-induced alterations observed in the open-field test were fully reversed, and those observed in the rotarod test were partially reversed, by physical exercise. Pain sensitivity was similar among all groups. Levels of reactive oxygen species and lipoperoxidation increased after ischemia; physical exercise decreased reactive oxygen species levels. None of the treatments altered the levels of antioxidant markers. In summary, ischemia-reperfusion resulted in motor impairment and altered striatal oxidative balance in this animal model, but those changes were moderated by physical exercise.

Pituitary Macroadenoma on 99mTc-TRODAT-1 Brain SPECT

Dopamine transporter (DAT) radiopharmaceuticals are capable of binding to the DAT with high selectivity, especially in the corpora striata, and have been widely used to evaluate parkinsonian disorder. However, only a few reports have mentioned about the extrastriatal pathologic DAT uptake. Herein we present an interesting case about the incidental discovery of pituitary macroadenoma with intense uptake of 99mTc-TRODAT-1.

Correlations between behavioural and oxidative parameters in a rat quinolinic acid model of Huntington’s disease: Protective effect of melatonin

The present study was designed to examine the correlations between behavioural and oxidative parameters in a quinolinic acid model of Huntington’s disease in rats. The protective effect of melatonin against the excitotoxicity induced by quinolinic acid was investigated. Rats were pre-treated with melatonin (5 or 20mg/kg) before injection of quinolinic acid (240nmol/site; 1μl) into their right corpora striata. The locomotor and exploratory activities as well as the circling behaviour were recorded. The elevated body swing test was also performed. After behavioural experiments, biochemical determinations were carried out. Melatonin partially protected against the increase of circling behaviour caused by quinolinic acid injection. No alteration was found in the number of crossings and rearings of animals treated with melatonin and/or quinolinic acid. Melatonin decreased the percentage of contralateral biased swings induced by quinolinic acid. Melatonin protected against the increase in reactive species and protein carbonyl levels as well as the inhibition of superoxide dismutase activity resulting from quinolinic acid injection. Melatonin was partially effective against the inhibition of striatal catalase activity and a decrease of non-protein thiol levels induced by quinolinic acid. Melatonin was not effective against the inhibition of Na+, K+ ATPase activity caused by quinolinic acid injection. There were significant correlations between circling behaviour and oxidative parameters. The antioxidant property of melatonin is involved, at least in part, in its neuroprotective effect. The results reinforce the idea that melatonin could be useful in overwhelming neurotoxicity caused by quinolinic acid, a rat model of Huntington’s disease.

Protective effect of N,N′-dialkylated analogs of 4,4′-diaminodiphenylsulfone in a model of intrastriatal quinolinic acid induced-excitotoxicity

The bacteriostatic agent 4,4′-diaminodiphenylsulfone or dapsone (DDS) and some of its N,N′-dialkylated analogs have shown anticonvulsant and neuroprotective properties in different experimental models. In this study, we tested the ability of five DDS analogs (N,N′-dimethyldapsone, N,N′-diethyldapsone, N,N′-dipropyldapsone, N,N′-dibutyldapsone and N,N′-ditosyldapsone) to attenuate quinolinic acid-induced toxicity in vivo. Male Wistar rats were treated with either DDS or analogs (12.5mg/kg and equimolar doses respectively) 30min before quinolinic acid intrastriatal stereotaxic injection (240nmol/μl). Six days after injury, circling behavior was evaluated by counting ipsilateral turns for 1h after apomorphine challenge (1mg/kg, sc). Twenty-four hours later, rats were sacrificed and their corpora striata were dissected out to determine GABA content. Hemotoxicity of the analogs was assessed as the ability to produce methemoglobin (MHb) in vivo. Blood was sampled from tail vein within 18h after drugs administration. Methemoglobin levels were determined by visible spectrophotometry and mean profiles of MHb-percentage versus time were obtained. All of the analogs tested decreased the number of ipsilateral turns/hour, reducing up to 67% the turns counting (p<0.05) when compared to those induced in animals receiving quinolinic acid with no treatment. N,N′-dimethylated, N,N′-diethylated and N,N′-dibutylated analogs significantly prevented the decrease of intrastriatal GABA content (p<0.05). Methemoglobin produced by the administration of analogs was significantly lower than the levels of the group receiving dapsone (p<0.05). The neuroprotective effect of analogs and their diminished hemotoxicity make them potential candidates for therapeutic applications.

Lewy body pathology and typical Parkinson disease in a patient with a heterozygous (R275W) mutation in the Parkin gene (PARK2)

There are only two reports of neuropathological findings in heterozygotes for Parkin (PARK2) mutation [3, 5]. One was a normal individual bearing an exon 3 deletion, who at autopsy (at age 93) revealed the absence of a-synuclein pathology and no neuronal depletion in the substantia nigra (SN). The other case carried a single point mutation (C212Y, exon 6) and had been affected by neuropathologically confirmed PSP. We here report a patient with a heterozygous Parkin mutation (R275W, on exon 7), clinical features of typical Parkinson’s disease and a neuropathological picture of diffuse Lewy body disease. This patient had two offspring with compound heterozygous (R275W and exon 3 deletion) Parkin mutations (Fig. 1), both of which were affected by early-onset PD ([6], family 48). To our knowledge, this is the first report of diffuse Lewy body pathology associated with clinically typical PD in a patient with a heterozygous Parkin mutation. A 62-year-old man presented with asymmetric fine motor impairment and rigidity, which were followed by resting tremor. There was good, sustained response to levodopa. Single photon emission computed tomography with Ioflupane (SPECT-DaTSCAN), performed 14 years from disease onset, showed severe reduction in tracer uptake in the corpora striata (Fig. 2a). Fifteen years after disease onset, the patient gradually became demented. This was confirmed by neuropsychological testing (MMSE 19/30; ADL 2; IADL 2), while neuroimaging at this time showed diffuse atrophy on brain MRI (Fig. 2b) and diffuse cortical and subcortical hypoperfusion on ECD-Tc99mSPECT. He died at the age of 80. At autopsy, macroscopic examination of the brain revealed bilateral depigmentation of the SN and locus

Progressive obtundation in a young woman with bilateral corpus striatum infarction: a case report

BackgroundBilateral ischemic infarction involving the corpus striatum is a rare event which usually results from global cerebral hypoxia, intoxications, and drug abuse.Case presentationWe report a 28 year old Caucasian woman who presented with progressive obtundation and later development of severe expressive dysphasia and Parkinsonism after sustaining ischemic stroke of both corpora striata. Hemorrhagic transformation developed on day four of admission.ConclusionThis is a rare case of bilateral basal ganglia infarction with hemorrhagic transformation in a young patient. Our patient's work up did not reveal any cause behind this stroke; however, advanced investigations (such as genetic testing and conventional angiography) were not done. The damage resulted in motor dysphasia and Parkinsonism. Neither dystonia nor other involuntary movements developed, and cognitive function was not assessed because of the language disorder.

RISQUE CHIMIQUE DANS LE BATIMENT. Premiere session : Actualites

The present study was designed to examine the correlations between behavioural and oxidative parameters in a quinolinic acid model of Huntington’s disease in rats. The protective effect of melatonin against the excitotoxicity induced by quinolinic acid was investigated. Rats were pre-treated with melatonin (5 or 20 mg/kg) before injection of quinolinic acid (240 nmol/site; 1 μl) into their right corpora striata. The locomotor and exploratory activities as well as the circling behaviour were recorded. The elevated body swing test was also performed. After behavioural experiments, biochemical determinations were carried out. Melatonin partially protected against the increase of circling behaviour caused by quinolinic acid injection. No alteration was found in the number of crossings and rearings of animals treated with melatonin and/or quinolinic acid. Melatonin decreased the percentage of contralateral biased swings induced by quinolinic acid. Melatonin protected against the increase in reactive species and protein carbonyl levels as well as the inhibition of superoxide dismutase activity resulting from quinolinic acid injection. Melatonin was partially effective against the inhibition of striatal catalase activity and a decrease of non-protein thiol levels induced by quinolinic acid. Melatonin was not effective against the inhibition of Na+, K+ ATPase activity caused by quinolinic acid injection. There were significant correlations between circling behaviour and oxidative parameters. The antioxidant property of melatonin is involved, at least in part, in its neuroprotective effect. The results reinforce the idea that melatonin could be useful in overwhelming neurotoxicity caused by quinolinic acid, a rat model of Huntington’s disease.

多系統萎縮症との鑑別を要した多腺性自己免疫症候群関連パーキンソン症候群の1例

A 76-year-old woman experienced unsteadiness in walking in 1996. On the basis of clinical and imaging findings, the patient was diagnosed multiple system atrophy. During follow-up, her gait disturbance became aggravated leaving her unable to walk unaided. She was referred to our department in 2003. T2-weighted images on brain magnetic resonance imaging (MRI) revealed low signal intensity in both putamina and a linear high-signal-intensity area on their outsides. Single photon emission computed tomography (SPECT) disclosed a reduced blood flow in both corpora striata. These findings were consistent with the diagnosis of Parkinsonian-type multiple system atrophy. The patient had anti-glutamic acid decarboxylase (GAD) antibody-positive type 1 diabetes mellitus and a normal thyroid function, and was positive for antithyroid antibodies. She was not found to have anemia on blood tests, but was positive for intrinsic factor antibodies. Vitamin B12 was markedly reduced to below the detection limit. The findings suggested that the patient's condition was autoimmune polyglandular syndrome type 3. In 2004, treatment with intramuscular injection of vitamin B12 was initiated, after which the patient's gait disturbance was improved and she was able to walk unaided. In 2009, her unsteady gait returned and was again unable to walk unaided. Autoimmune encephalopathy was suspected, and thus high-dose intravenous immunoglobulin therapy was performed. Following treatment she was able to walk steadily. This case suggests the importance of detailed tests for autoantibodies, including endocrine autoantibodies, and the measurement of vitamin B12 and total homocysteine levels in view of the possibility of autoimmune polyglandular syndrome-related neurological disorders in diabetic patients with intractable neurological disorders that are difficult to diagnose.

A functional MRI study of the brain in stroke patients with upper-limb paralysis treated with constraint-induced movement therapy

Objective To investigate and compare the activation patterns of stroke patients with upper-limb paralysis using functional MRI before and after treatment with constraint-induced movement therapy (CIMT) so as to explore the mechanism of CIMT. Methods Six patients in chronic stage of brain infarction who have functional disturbance in fight upper-limb and 9 normal controls were entered into the study. All of the patients were asked to perform the thumb-to-index finger tapping task and underwent functional MRI before and two weeks after CIMT. The controls underwent fMR[of same protocol once. The patients' upper-Limb function scores before and after CIMT were analyzed with SPSS 11.5 by paired t test.The fMRI data were analyzed with analysis of functional neurolmages (AFNI) software. The percentage of blood oxygenation level dependent (BOLD) signal change for the normal control was analyzed by one-sample t test to indentify the activated brain regions. The percentage change of BOLD signal for the patients before and after CIMT was compared to control's data by independent-samples t test. The percentage change of BOLD signal for the patients before and after CIMT was analyzed by paired-samples t test. The significant difference level was set P <0. 05. Results The fMRI showed the patients' activated brain regions before CIMT were similar to that of the controls', while the activation level was lower. There were wide areas activated to compensate the impaired function especially for the right upper-limb. Before CIMT, the patients' score for right upper-limb on the action research arm test was 27±4. After CIMT, the patients' score was 40±3, and the difference was significant(t=14. 626, P <0. 05), which indicated the improved function. These subjects also displayed cortical reorganization after CIMT on fMRI. The areas responsible for the right hand movement showed increased activation and the activation level at bilateral corpora striata thalami, and cerebella increased. There were also activated regions in the eontralateral parietal lobe. Conclusions CIMT can improve the patients' upper-limb function effectively. The constraint-induced movement of the affected arm during CIMT appears to induce cortical reorganization and compensation as measured by fMRL Key words: Cerebrovascular accident; Magnetic resonance imaging; Hemiplegia; Exercise therapy

Modulation in acetylcholinesterase of rat brain by pyrethroids in vivo and an in vitro kinetic study.

The modulation of acetylcholinesterase (AChE) of rat brain by two pyrethroids--permethrin (PM) and cypermethrin (CPM)--was studied both in vivo and in vitro. PM inhibited AChE activity in all regions of the rat brain (cerebral cortex, cerebellum, corpora striata, brain-stem, hippocampus, and hypothalamus) at 4, 8, and 12 h after gastric intubation, whereas CPM elevated the enzyme activity in vivo. Substrate-dependent enzyme kinetic studies have shown that PM and CPM behave as mixed-type inhibitors, as evidenced by alterations in both Michaelis-Menten constant (Km) and maximal velocity (Vmax) values. This indicates that both PM and CPM and substrate acetylcholine interact at hydrophobic subsites and may be able to bind simultaneously to the enzyme.

Loss of D2 receptors during aging is partially due to decreased levels of mRNA

Corpora striata of old rats (24-25 months) contain only about half as much mRNA for D2 dopamine receptors as those of young (6 months) counterparts. This reduction can be observed by in situ hybridization of brain slices as well as with Northern and dot blot analyses of striatal extracts. Decreased levels of D2 receptor mRNA as described in this study are consistent with reductions in receptor containing neurons (20%) and receptor biosynthesis (40%), as previously observed in this and other laboratories. Thus, age related changes in D2 receptor gene expression appear to be partially responsible for loss of these receptors.

A regional study of sex differences in rat brain serotonin

Carlsson, Maria and Arvid Carlsson: A regional study of sex differences in rat brain serotonin. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1988, 12 : 53–61. 1. 1. Male and female rats were compared with respect to serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), tryptophan, dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxytyramine (3-MT) levels in five brain regions (brainstem, hypothalamus/preoptic area, corpora striata, limbic forebrain and cortex). Brain 5-HT synthesis rate was also studied in the two sexes. 2. 2. There were no consistent gender differences in the dopaminergic system. 3. 3. In contrast, the serotonergic system was more expressed in females: 5-HT levels were significantly higher in females than in males in the brainstem and limbic forebrain and tended to be so in the cortex. 5-HIAA levels were significantly higher in females in all five brain regions. The 5-HIAA/5-HT ratios were significantly higher in females in the hypothalamus/preoptic area and limbic forebrain and tended to be so in the striatum and cortex. Tryptophan concentrations were significantly higher in females in the brainstem, striatum and cortex. In no brain region were 5-HT, 5-HIAA or tryptophan levels higher in males. Following L-amino acid decarboxylase inhibition 5-hydroxytryptophan (5-HTP) accumulation was more pronounced in the female rat brain. 4. 4. Taken together these results suggest that the brain 5-HT system has a higher potential in female than in male rats. This sex difference is not restricted to a specific region but seems to exist generally in the brain.

2,4-Pentanedione: 9-Day and 14-week vapor inhalation studies in Fischer-344 rats

Fischer-344 rats, in groups of 10 males and 10 females, were exposed for 9 days (6 hr/day) to 2,4-pentanedione (2,4-PD) vapor at mean concentrations of 805, 418, 197, and 0 (control) ppm. No deaths occurred, and the only adverse signs were of sensory irritation (partial closure of eyelids, periocular and perioral wetness) at 805 ppm. Also at 805 ppm were decreased body and organ weights, lymphocytosis, and moderate inflammation of the nasal mucosa. At 418 ppm there was a decrease in body weight gain and mild inflammation of the nasal mucosa. Apart from minimal nasal mucosal inflammation, there were no effects at 197 ppm. In the subchronic (14-week) study, rats were exposed (6 hr/day; 5 days/week) to 650, 307, 101, and 0 (control) ppm of 2,4-PD vapor, using groups containing 20 males and 20 females, with half being sacrificed at the end of the exposure period and the remainder kept for a 4-week postexposure recovery period. An additional 10 males were added to the 650 and 0 ppm groups for glutaraldehyde perfusion and subsequent electron microscopic examination of sciatic nerves. At 650 ppm, all females and 10 of 30 males died between the second and sixth weeks of exposure. These animals had acute degenerative changes in the deep cerebellar nuclei, vestibular nuclei and corpora striata, and acute lymphoid degeneration in the thymus. Seven of 15 male survivors of the 650 ppm group (combined 14-week and recovery sacrifices) had gliosis and malacia in the same brain regions, minimal squamous metaplasia in the nasal mucosa, decreased body and organ weights, lymphocytosis, and minor alterations in serum and urine chemistries. No ultrastructural evidence of peripheral neuropathy was observed. Except for central neuropathy, many of the adverse effects at 650 ppm were less marked in the 4-week recovery animals. No deaths occurred at 307 ppm, but females had slightly decreased body weight gains, and in both sexes there were minor alterations in hematology, serum chemistry, and urinalysis parameters, which were not present in the 4-week recovery animals. Rats exposed to 101 ppm showed no differences from the control rats. Subchronic exposure to 650 ppm of 2,4-PD vapor causes serious adverse biological effects. Under these study conditions, the minimum-effects concentration was 307 ppm, and the no-adverse effects concentration was 101 ppm.

2,4-Pentanedione: 9-Day and 14-Week Vapor Inhalation Studies in Fischer-344 Rats

2,4-Pentanedione: 9-Day and 14-Week Vapor Inhalation Studies in Fischer-344 Rats. DODD, D.E., GARMAN, R.H., PRITTS, I.M., TROUP, C.M., SNELLINGS, W.M, AND BALLANTYNE, B. (1986). Fundam. Appl. Toxicol. 7, 329–339. Fischer-344 rats, in groups of 10 males and 10 females, were exposed for 9 days (6 hr/day) to 2,4-pentanedione (2,4-PD) vapor at mean concentrations of 805, 418, 197, and 0 (control) ppm. No deaths occurred, and the only adverse signs were of sensory irritation (partial closure of eyelids, periocular and perioral wetness) at 805 ppm. Also at 805 ppm were decreased body and organ weights, lymphocytosis, and moderate inflammation of the nasal mucosa. At 418 ppm there was a decrease in body weight gain and mild inflammation of the nasal mucosa. Apart from minimal nasal mucosa] inflammation, there were no effects at 197 ppm. In the subchronic (14-week) study, rats were exposed (6 hr/day; 5 days/week) to 650, 307, 101, and 0 (control) ppm of 2,4-PD vapor, using groups containing 20 males and 20 females, with half being sacrificed at the end of the exposure period and the remainder kept for a 4-week postexposure recovery period. An additional 10 males were added to the 650 and 0 ppm groups for glutaraldehyde perfusion and subsequent electron microscopic examination of sciatic nerves. At 650 ppm, all females and 10 of 30 males died between the second and sixth weeks of exposure. These animals had acute degenerative changes in the deep cerebellar nuclei, vestibular nuclei and corpora striata, and acute lymphoid degeneration in the thymus. Seven of 15 male survivors of the 650 ppm group (combined 14-week and recovery sacrifices) had gliosis and malacia in the same brain regions, minimal squamous metaplasia in the nasal mucosa, decreased body and organ weights, lymphocytosis, and minor alterations in serum and urine chemistries. No ultrastructural evidence of peripheral neuropathy was observed. Except for central neuropathy, many of the adverse effects at 650 ppm were less marked in the 4-week recovery animals. No deaths occurred at 307 ppm, but females had slightly decreased body weight gains, and in both sexes there were minor alterations in hematology, serum chemistry, and urinalysis parameters, which were not present in the 4-week recovery animals. Rats exposed to 101 ppm showed no differences from the control rats. Subchronic exposure to 650 ppm of 2,4-PD vapor causes serious adverse biological effects. Under these study conditions, the minimum-effects concentration was 307 ppm, and the no-adverse effects concentration was 101 ppm.

Effects of chronic ingestion of alcohol in the pregnant rat on catecholamine-sensitive adenylate cyclase in the brain of mothers and their offspring

To study the effects of maternal alcohol ingestion on brain adenylate cyclase in offspring, rats were given ethanol in the drinking water before, during and after gestation. Fifteen-day-old pups from alcoholic mothers had reduced body and wet brain weight and protein content with normal concentrations of DNA and RNA in brain; pups from mothers deprived of alcohol from the 21st day of gestation had normal growth and brain protein, DNA, RNA and cyclic nucleotide concentrations. Adenylate cyclase activity was less in homogenates from the diencephalon, mesencephalon and cerebellum of alcoholic and alcohol-deprived mothers than in the corresponding homogenates from control mothers. A reduction of the enzyme activity was only observed in homogenates from diencephalon of offspring from alcoholic and alcohol-deprived mothers as compared with controls. Sensitivity of adenylate cyclase to noradrenaline was reduced in the corpora striata and diencephalon from alcoholic mothers, while these changes were absent in alcohol-deprived mothers and their offspring. Ingestion of ethanol in pregnant mothers does not seem to effect significantly the adenylate system in the brain of the offspring.

Fetal and postnatal development of cyclic GMP phosphodiesterase activity in the rat brain

Cyclic GMP concentration and cyclic GMP phosphodiesterase activity were studied in rat mothers and fetuses at 17, 19 and 21 days of intrauterine life and 0, 1, 4, 10, 15,20, 30 and 45 days after birth. During this developmental period, the increase in cyclic GMP concentration was discrete and the value in 15-day-old rats was already similar to the adult level. Cyclic GMP phosphodiesterase activity increased from 17- to 19-day fetuses and was significantly reduced in 21-day fetuses, neonates, and 1-day-old rats. This reduction may be a result of fetal endocrine preparation for parturition. During postnatal development, cyclic GMP phosphodiesterase activity increased in a parallel way in the limbic system, corpora striata, cerebral hemispheres, and diencephalon, reaching maximal level between 20 and 30 days after birth, and then decreasing to the adult value. The highest activity was found in corpora striata and the lowest in diencephalon. Cerebellar cyclic GMP phosphodiesterase activity was very high in the 4-day-old rat (257% of adult value) and diminished significantly in the 10-day-old rat with no subsequent changes. Kinetic analysis of the enzyme during postnatal forebrain development showed an increase in both the V max and the apparent K m. A decrease in the enzyme's V max was observed only in the cerebellum. The importance of cyclic GMP phosphodiesterase regulation of cyclic GMP concentrations in the brain during development is discussed.

Age- and sex-related changes of tryptophan accumulation in discrete areas of the rat brain

Summary Aging is known to involve changes in the neurochemistry of catecholaminergic and serotonergic components of the brain. With regard to the serotonin precursor L-tryptophan, the experiments performed in this study show that, independently of the age and sex of the animals the greatest tryptophan uptake is constantly seen in the lower brainstem, corpora striata, amygdala-hippocampus and hemispheres. However, tryptophan accumulation by the brain is more active in some brain areas of old female rats than in those of their old male mates.

Immunoperoxidase Localization of Morphine in the Rat Basal Ganglia

AbstractA procedure has been developed for the immunohistochemical localization of morphine in the rat basal ganglia. Corpora striata of Sprague-Dawley rats, treated with morphine sulfate subcutaneously, were removed and quick frozen in isopentane/liquid nitrogen. Five μm sections were reacted with various dilutions of goat anti-morphine serum (IgG), rabbit anti-sheep and rabbit anti-goat peroxidase-labeled IgG, diaminobenzidine and counterstained with methyl green. Light microscopic presence of dark brown reaction product indicated positive staining. Diffuse and particulate cytoplasmic and plasmalemmal staining were observed. Nonspecific background staining was substantially eliminated by adsorbing the morphine antiserum with lyophilized rat brain followed by DEAE-cellulose chromatography prior to the immune reactions. The technique utilizes a two-stage conjugation reaction employing peroxidaselabeled immunoglobulin.

Long‐term administration of L‐DOPA does not damage dopaminergic neurons in the mouse

To examine the possibility that long-term L-DOPA therapy may be toxic to and destroy nigrostriatal dopaminergic neurons, mice were given large doses of L-DOPA (200 mg per animal per day) for 18 months. L-DOPA treatment was then discontinued to allow washout of drug from brain; 8 days later, L-DOPA was undetectable in corpora striata. Biochemical indices of the integrity of nigrostriatal neurons (striatal dopamine and DOPAC concentrations and activities of tyrosine hydroxylase and DOPA decarboxylase) were equal in DOPA-treated and control mice, suggesting that prolonged L-DOPA administration did not damage nigrostriatal neurons.

Dopamine-sensitive adenylate cyclase in homogenates of rat striata during ethanol and barbiturate withdrawal.

Repeated administrations of ethanol and of phenobarbital to rats led to characteristic withdrawal symptoms when the drug had been stopped. Since both drugs affect brain dopamine metabolism, the postjunctional sensitivity to dopamine in the corpora striata was tested during ethanol or phenobarbital withdrawal. This was done by studying the dopamine-sensitive adenylate cyclase in homogenates of the copora striata of ethanol- or phenobarbital-dependent rats. The results demonstrated a slight postjunctional subsensitivity to dopamine in withdrawal from both ethanol and phenobarbital. Both drugs, when added in vitro, did not affect the postjunctionsl sensitivity to dopamine. The results do not support the hypothesis, at least not in the case of dopamine, that a postjunctional supersensitivity to neurotransmitters is important for withdrawal symptoms after chronic administration of drugs inducing physical dependence.