Effects on homeostasis of intraventricular injections of 6-hydroxydopamine in rats.

Data from a series of experiments with male albino Sprague-Dawley rats show that intraventricular injections of 6-hydroxydopamine after pretreatment with desmethylimipramine and pargyline, or pargyline alone, produced severe depletions of brain dopamine. Like Ss with lateral hypothalamic damage, these Ss became aphagic and adipsic, showed prolonged periods of anorexia before they again accepted dry chow and water, maintained relatively low body weights, no longer increased food intakes after injection of 2-deoxy-dextroglucose, and delayed drinking to thirst stimuli. However, unlike recovered laterals, they did not have marked impairments of feeding efficiency, learned taste aversions, or thermoregulation during heat stress. Results suggest that brain catecholamines play an important role in some regulatory processes, but that lateral hypothalamic lesions may not be tantamount to destruction of the dopamine-containing neurons of the nigrostriatal pathway. (4? p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of intraventricular and intraspinal 6-hydroxydopamine on blood pressure of renal hypertensive rats

6-Hydroxydopamine (6-OH-DA) was administered into the lateral brain ventricle of normal rats and of rats with renal hypertension produced by unilateral clipping of the renal artery, and was also administered into the spinal cord of normal rats. Intraventricular administration of 6-OH-DA prevented the development of renal hypertension in rats, but was ineffective in developed renal hypertension. The development of renal hypertension was not affected by pretreatment with intraspinal injection of 6-OH-DA, which produced a marked reduction only in spinal cord noradrenaline. These data suggest that brain adrenergic neurones may participate in the production of renal hypertension but the noradrenergic projections in the spinal cords are not essential for this process.     

Central noradrenergic neurons: Differential effects on body weight of electrolytic and 6-hydroxydopamine lesions in rats.

Compared the effects of bilateral electrolytic and 6-hydroxydopamine (6-OHDA) lesions of the ventral noradrenergic bundle (VB) in 2 experiments with a total of 67 female albino rats. When Ss were fed only a standard laboratory diet, no significant differences were found between groups. When a high-fat diet supplement was introduced, the group with electrolytic lesions became significantly heavier than the control group; however, the 6-OHDA group did not differ from the controls. Norepinephrine depletion was significantly greater following the 6-OHDA than the electrolytic lesions. Both lesions reduced telencephalic dopamine and serotonin only slightly. Exp II, in which both types of lesions were placed at a rostral ventromedial hypothalamic site, yielded the same pattern of results. Diet-dependent increased in body weight were attributed to the destruction of a non-noradrenergic system, which was spared by the relatively selective 6-OHDA lesion but damaged by the nonselective electrolytic lesion. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of intracisternal 6-hydroxydopamine treatment on acquisition and performance of rats in a double T-maze.

136 male Sprague-Dawley rats in 4 experiments were subjected to various treatments with 6-hydroxydopamine (6-OHDA) to produce decrements in brain catecholamine content either before or after learning to respond in an appetitively motivated double –T maze task. Intracisternal injections of 6-OHDA not only impaired acquisition of the required behavioral response but also decreased performance of Ss which had previously acquired the task. Although reduced food consumption found in 6-OHDA-treated Ss may contribute to the observed deficits in –T maze responding, the behavioral deficit produced by 6-OHDA injection did not seem to be due only to a simple decrease in food intake. The decrements in acquisition and performance were clearly related to amount of central catecholamine depletion produced by 6-OHDA treatment. Further analysis suggested that the behavioral deficits were more related to the reductions in dopamine than they were to the depletion of brain norepinephrine. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Simultaneous transplantation of fetal mesencephalic cells to the striatum and globus pallidus of rats with lesions induced by 6-hydroxydopamine

INTRODUCTION: Studies of neural transplants in experimental models of Parkinson's disease have concentrated their attention on ectopic transplants of foetal mesencephalic cells to denervated striatum. However, the external globus pallidus has recently been shown to play an important part in the physiopathology of this disease. OBJECTIVE: Bearing in mind the importance of loss of extra-striatal dopamine in the genesis of the clinical signs found in parkinsonism, the objective of this study was to evaluate the effect of foetal mesencephalic transplantation to the globus pallidus of hemiparkinsonian rats. MATERIAL AND METHODS: Following conventional transplantation methodolgy, suspensions of cells from the ventral mesencephalum of rat embryos (E-14) were implanted. The tissue was grafted into the striatum, pallidum-striatum and pallidum areas of rats with unilateral lesions of the striatonigral bundle. One, two, three and six months after transplantation, the rotatory activity induced by D-amphetamine was evaluated. The rotatory behaviour induced by apomorphine was evaluated at three months. Motor ability of the front legs was evaluated in all experimental groups three months after transplantation using the 'ladder test'. RESULTS: In the experimental groups in which a transplant was made to the globus pallidus there was a significant reduction (p < 0.01) in rotatory activity induced by D-amphetamine and by apomorphine as compared with the non-transplanted groups. CONCLUSIONS: Transplants of foetal dopaminergic cells survive in the globus pallidus of hemiparkinsonian rats and can improve the rotational activity induced by dopaminergic agonists.     

Behavioral evaluation of the unilateral lesion model in rats using 6-hydroxydopamine. Correlation between the rotations induced by D-amphetamine, apomorphine and the manual dexterity test

INTRODUCTION: Evaluation of rotatory activity induced by dopaminergic agonists is the most widely used test of conduct for the measurement of dopaminergic depletion of a unilateral lesion of the striatonigral pathway caused by 6-hydroxydopamine (6-OHDA) in rats, since it is quantitatively related to the extension of the dopaminergic denervation. OBJECTIVE: The objective of this study was to evaluate, from different angles, the changes in conduct seen in the model of unilateral lesion with 6-OHDA and to establish correlation with the rotation induced by D-amphetamine and by apomorphine and the ladder test. MATERIAL AND METHODS: Male Wistar rats were used. Lesions were produced in the SNpc by stereotactic injection of 6-OHDA into the right hemisphere and the effectiveness of the lesions was studied using the rotary conduct induced by D-amphetamine and apomorphine. The motor ability of the front legs was measured by the ladder test, carried out under standard and forced conditions. RESULTS: All the animals with lesions had difficulty in reaching food with both legs, although the most pronounced deficit was in the leg contralateral to the lesion. The ladder test correlated better with rotatory activity induced by apomorphine than by D-amphetamine. CONCLUSION: The animals with most dopamine loss showed most deficient use of their front legs.     

Effects of 6-hydroxydopamine lesions of the nucleus accumbens septi and olfactory tubercle on feeding, locomotor activity, and amphetamine anorexia in the rat.

In Exp I with 24 male albino Wistar rats, bilateral 6-hydroxydopamine lesions of the nucleus accumbens septi (NAS) and olfactory tubercle (OT) caused enhanced intake of wet mash in 23-hr-food-deprived Ss tested in photocell activity cages during restricted 30-min sessions. This mild hyperphagia was accompanied by a significant hypoactivity in the group with NAS/OT lesions. No hyperphagia was observed during a prolonged 120-min test session or in free-feeding tests conducted in the home cage. Anorexia induced by dextroamphetamine (.5 and 1.5 mg/kg) was unaltered by the lesion, although the locomotor stimulant action of the drug was attenuated. Results of Exp II, with 36 Ss, show that the NAS/OT lesion also enhanced food intake in the photocell cages during 30-min sessions with dry food pellets but that food-associated drinking was concomitantly reduced. Results are consistent with the hypothesis that the behavioral changes caused by mesolimbic neuron destruction result in part from an inability to switch from one behavioral activity to another. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of nigral implantation on sensitization to dopamine agonists in 6-hydroxydopamine-lesioned rats

The implantation of fetal nigral tissue into the striatum of patients with Parkinson's disease is a promising approach to treatment which may produce clinical benefit partly by influencing drug responsiveness. The purpose of the present study was to determine the pharmacological mechanisms which drug response changes by measuring to what extent sensitization produced by repeated apomorphine treatment was attenuated by tissue implantation in rats with nigrostriatal lesions. Prior to implantation of nigral cell suspensions, the daily administration of apomorphine to rats with unilateral 6-hydroxydopamine lesions produced a progressive increase in the magnitude and duration of rotational behaviour. After implantation, apomorphine-induced rotational effects were reduced to levels observed upon the initial exposure to drug and did not increase following repeated treatment. Attenuated responses to selective D1 and D2 agonists were also observed after implantation. In vehicle-implanted rats, the initial response to apomorphine was attenuated but then increased following repeated apomorphine administration. No attenuation in responses to selective D1 and D2 agonists was observed in this group. Cell suspensions prepared from fresh and cyropreserved tissue produced similar behavioural effects, even though the volume of transplanted striatum exhibiting tyrosine hydroxylase activity was greater with fresh tissue. The duration of rotational behaviour induced by apomorphine was not affected by cell implantation. These findings suggest that the expression of sensitization in an animal model of parkinsonism may disappear after a period without drug treatment. Implantation of nigral tissue may produce beneficial results in parkinsonism by limiting the development of dopamine agonist-induced sensitization.     

Effects of 6-hydroxydopamine and pimozide on temperature maintenance by the chicken

Intraventricular implants of pimozide in adult white leghorn hens were used to block dopamine (DA) receptors, and 6-hydroxydopamine (6-OHDA) was injected intraventricularly to destroy the noradrenergic system locally. The hens were exposed to ambient temperatures of 5 and 35 degrees C, and their core temperature was measured. One hundred micrograms of 6-OHDA significantly reduced the norepinephrine (NE) but not the DA content of the hypothalamus and reduced the uptake of [3H]NE but not of [3H]DA by synaptosomes in vitro. Neither of the drug treatments nor their combination affected average core body temperature (Tb) at either 5 or 35 degrees C. Pimozide treatment caused a lower maximum Tb at 35 degrees C and a higher maximum Tb at 5 degrees C than the control treatment. No evidence was obtained that 6-OHDA treatment affected body temperature regulation. It is concluded that neither the DA nor the NE system is essential for normal temperature maintenance in the hen exposed to either 5 or 35 degrees C.     

Correlation of apomorphine- and amphetamine-induced turning with nigrostriatal dopamine content in unilateral 6-hydroxydopamine lesioned rats

In the unilateral 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease, controversy exists concerning the use of apomorphine- or D-amphetamine-induced rotations as reliable indicators of nigrostriatal dopamine depletion. Our objective was to evaluate which, if either, drug-induced behavior is more predictive of the extent of nigrostriatal dopamine depletion. Fischer 344 and Sprague-Dawley rats were unilaterally injected with 9 micrograms/4 microliters/4 min 6-hydroxydopamine into the medial forebrain bundle. The animals were behaviorally tested with apomorphine (0.05 mg/kg, s.c.) and D-amphetamine (5.0 mg/kg, s.c.). Following testing, the brains were removed and the right and left striata, substantia nigra and ventral tegmental area were dissected free and quickly frozen at -70 degrees C for analysis of catecholamine content by high performance liquid chromatography coupled with electrochemical detection. Our results indicate that an animal which has greater than a 90% depletion of dopamine in the striatum might not rotate substantially on apomorphine, without a concomitant depletion of > 50% of the DA content in the corresponding substantia nigra. No correlations were seen involving depletions of the ventral tegmental area and the extent of the lesions to the striatum. Submaximally lesioned (75-90% depleted) rats were found to rotate on D-amphetamine but not on apomorphine. In addition, control rats that did not receive lesions were often seen to rotate extensively on D-amphetamine. We therefore conclude that maximal lesions of the striatum and substantia nigra are required to generate rotations demonstrable with low dose apomorphine but not with D-amphetamine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of reinforcement omission on rats with lesions in the amygdala.

Trained 12 male Wistar rats with bilateral lesions in the amygdala to barpress on an FI schedule of reinforcement. During test trials, when reinforcement was occasionally omitted, response rates of 12 controls increased in the subsequent interval, whereas lesioned Ss showed no significant change. In Exp II Ss received fixed-ratio reinforcement on 1 lever, which was followed by a time-out period and fixed-ratio reinforcement on a 2nd lever. Results indicate that after reinforcement was withheld Ss with damage in the amygdala did not increase responding in the subsequent time-out period, whereas controls showed significantly higher rates. Differential latencies to initiation of response after nonreinforcement were also found. The deficits following brain damage are attributed to a reduction in nonreinforcement-induced frustration. (20 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of lateral hypothalamic lesions on placentophagia in virgin, primiparous, and multiparous rats.

Produced lesions of the lateral hypothalamus (LH) in 25 pregnant and 25 nonpregnant Sprague-Dawley rats through chronically implanted electrodes to investigate the effect of LH damage on placentophagia. Other variables investigated were prior parturitional experience and stimulus properties of the placenta. Lesions were produced under either anesthesia 24 hr prior to parturition in pregnant Ss and 24 hr prior to placenta presentation in nonpregnant Ss. Lesions produced aphagia to a liquid diet. Pregnancy was not a significant variable in the initiation of placentophagia, but prior parturitional experience was critical. Virgin and primiparous Ss did not exhibit placentophagia following LH damage, but multiparous Ss would eat placenta whenever the opportunity arose, independently of LH damage and pregnancy. (18 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of lamotrigine and conventional antiepileptic drugs on amygdala- and hippocampal-kindled seizures in rats

A computer aided monitor-data processing system (CAMP-System) was developed in order to get a consistent and comprehensive database which can very precisely reflect intra-operative haemodynamic courses. The goal of the present study was to introduce a new method to scan and to gauge haemodynamic courses and to demonstrate its superiority over the traditional way of data processing based on a handwritten anaesthesia protocol. METHODS: The computerized system was applied to a study which was designed to investigate the influence of ketanserin (K) vs. urapidil (U) on haemodynamic stability during cardiac operations. Twenty male patients scheduled for myocardial revascularization received either 20 mg K or 30 mg U. Heart rate, central venous, arterial and pulmonary artery pressures were measured and on-line recorded every 20 seconds by the computer record system. In the handwritten protocol these variables were registered at eight pre-defined time points. Computerized data processing (including artifact depletion and data condensation) was compared to the results evaluated from the handwritten protocol. RESULTS: While the only significant differences in the handwritten protocol were slightly higher values of pulmonary artery pressures in group K, the computer analysis revealed a number of further differences. Higher maximum and a less stable time course of HR in group K in the pre-bypass phase and lower mean and standard deviation of MAP during cardiopulmonary bypass. CONCLUSION: Computerized data processing including automatic artifact suppression and data condensation was able to reveal differences in the course of haemodynamic variables that cannot be detected in a conventional handwritten protocol.     

Modulation of postural tremors at the wrist by supramaximal electrical median nerve shocks in essential tremor, Parkinson's disease and normal subjects mimicking tremor

The response of postural wrist tremors to supramaximal median nerve stimulation was examined in patients with hereditary essential tremor (n = 10) and Parkinson's disease (n = 9), and in normal subjects mimicking wrist tremor (n = 8). The average frequency of on-going tremor was the same in all three groups. Supramaximal peripheral nerve shocks inhibited and then synchronised the rhythmic electromyographic (EMG) activity of all types of tremor. The duration of inhibition ranged from 90 to 210ms, varying inversely with the frequency of on-going tremor. There was no significant difference in mean duration of inhibition or in the timing of the first peak after stimulation on the average rectified EMG records between the three groups. The degree to which supramaximal peripheral nerve shocks could modulate the timing of rhythmic EMG bursts in the forearm flexor muscles was also quantified by deriving a resetting index. No significant difference in mean resetting index of the three groups was found. These results suggest that such studies cannot be used to differentiate between the common causes of postural wrist tremors.     

Effects of local anesthesia on persistence of peripherally induced postural asymmetries in rats.

Hindlimb flexion induced by direct stimulation of the hindlimb has been previously observed subsequent to spinal section if an appropriate time interval was allowed to elapse between onset of flexion and spinal cord section. The present 3 experiments tested the possibility that asymmetry persistence is a product of ongoing cutaneous input that continues after stimulation offset and spinal cord section. A local anesthetic (lidocaine; 25 mg/kg, sc) was injected into the general area of stimulation in 65 hooded rats, and its effects on asymmetry were assessed. Results generally indicate that ongoing cutaneous input is not a sufficient explanation for persistence of flexion in stimulated Ss with intact or severed spinal cords. Data reveal, however, that ongoing cutaneous input may partially explain results of a previous study by the 1st author et al (see record 1982-23053-001) that employed a "stimulation-wait" preparation to obtain peripherally induced spinal fixation. (9 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

7-nitroindazole attenuates 6-hydroxydopamine-induced spatial learning deficits and dopamine neuron loss in a presymptomatic animal model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder in which loss of dopaminergic (DA) neurons (>50%) in the substantia nigra (SN) precedes most of the overt motor symptoms, making early diagnosis and treatment interventions difficult. Because PD has been associated with free radicals generated by nitric oxide, this study tested whether treatments of 7-nitroindazole (7NI), a nitric-oxide-synthase inhibitor, could reduce cognitive deficits that often emerge before overt motor symptoms in a presymptomatic rat model of PD. Rats were given intraperitoneal injections of 50 mg/kg 7NI (or vehicle) just before receiving bilateral, intrastriatal injections of the DA-toxin, 6-hydroxydopamine (6-OHDA). The rats were then given a battery of motor tasks, and their learning ability was assessed using a spatial reversal task in a water-T maze. Results indicate that 7NI treatments attenuate 6-OHDA-induced spatial learning deficits and protect against DA cell loss in the SN, suggesting that 7NI may have potential as an early, presymptomatic pharmacotherapy for PD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of context manipulation on memory and reversal learning in rats with hippocampal lesions.

Conducted 3 experiments with 83 male Long-Evans rats to investigate (a) the memory of hippocampus-damaged Ss, and (b) their ability to modify response strategies in relation to the influence of familiar contextual cues. In Exp I, groups of hippocampal and control Ss learned a simultaneous discrimination habit and were subsequently tested for its retention under variable contextual conditions. All groups recalled the discrimination response to an equally high level when testing conditions were constant throughout, but the hippocampal group showed impaired memory when contextual stimuli at recall testing did not conform to those of original learning. Results of Exp II indicate that the hippocampal impairment was not simply the result of introducing novel stimuli. In Exp III, Ss were administered a reversal learning task with contextual stimuli varied between the 2 tests. The typically observed impairment of hippocampal Ss on this task was reduced by contrasting contextual conditions. Results are seen to support a context-retrieval interpretation of hippocampal function. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)