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Biomedical subjects

R J Mandel

Publications and source records attributed to R J Mandel.

46 records · Page 3Linked to original sources
PubMed1990

Bromocriptine-induced rotation: characterization using a striatal efferent lesion in the mouse.

Two lesion techniques were used to elucidate the mode of action of bromocriptine (BRC)-induced behavior in mice. With the first lesion, a unilateral 6-hydroxydopamine (6-OHDA) preparation, BRC administration resulted in contralateral rotation which was blocked by alpha-methyl-para-tyrosine (AMPT), comparable to previous reports using rats. After striatonigral/entopeduncular lesion, mice did not rotate in response to doses of BRC up to 30 mg/kg but did show general activation which was also inhibited by AMPT pretreatment. It is concluded that BRC does not elicit rotation when there is no dopaminergic asymmetry such as that caused by a unilateral 6-OHDA lesion or no asymmetry in the striatonigral or striatoentopeduncular efferents. Since BRC-induced behaviors are dependent on intact presynaptic dopamine and BRC is predominantly a D-2 agonist, behaviors elicited in response to BRC must be the result of coactivation of D-1 receptors by endogenous dopamine. Thus, the behavioral effects of BRC, and perhaps D-2 agonists in general, must be mediated by efferents other than the striatonigral and striatoentopeduncular pathways.

Animals↗
PubMed1989

Enhanced detection of nucleus basalis magnocellularis lesion-induced spatial learning deficit in rats by modification of training regimen.

Bilateral excitotoxic lesions of the nucleus basalis magnocellularis (NBM) in the rat cause deficits in the water maze, a spatial memory paradigm. Previous investigations aimed at reversing the water maze performance deficit with anticholinesterase treatments have been unable to demonstrate a consistent drug effect due to the relatively good acquisition of the task seen following NBM lesions. The present investigation tested three different water maze training regimens designed to separate the learning curves. F-344 rats received bilateral NBM injections of ibotenic acid; sham-operated rats served as controls. The animals were tested in three groups in the water maze as follows: (1) four trials per day with no intertrial interval (standard paradigm), (2) four trials per day with a 10-minute intertrial interval, and (3) two trials per day with no intertrial interval. Each group was tested in the water maze for five consecutive days, followed by two days of rest, and then tested for an additional five days. The two-trial per day paradigm was more difficult than the standard paradigm for both lesions and controls and yielded the most difference between lesions and controls as compared to the other two testing regimens. The 10-min intertrial interval schedule was more difficult than the standard paradigm for lesioned animals but acquisition was not affected in control rats. These data demonstrate that the nucleus basalis lesions cause a deficit in the water maze task regardless of training parameters. Further, while all rats showed some acquisition of the water maze task, training schedule affected the level of learning of both lesioned and control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Spatial learning in rats: correlation with cortical choline acetyltransferase and improvement with NGF following NBM damage.

Rats display an acquisition deficit in a circular water maze following excitotoxic lesions of the nucleus basalis magnocellularis (NBM). Experiments were therefore performed to determine if acquisition behavior on this task could predict the degree of cortical cholinergic deafferentation and if the acquisition deficit could be pharmacologically reversed. Performance on acquisition was highly correlated with the lesion-induced reduction in cortical choline acetyltransferase (ChAT) activity. Accuracy of spatial behavior was highly correlated to percentage ChAT depletion (r = 0.75). Neither lesioned rats nor controls displayed a retention deficit after a 9-day interval, nor did either group display a passive-avoidance retention deficit. To test the causal relationship between cholinergic dysfunction and spatial behavior, the central nervous system cholinergic enhancer nerve growth factor (NGF) was intraventricularly infused for 4 weeks. NGF infusion resulted in improved acquisition of the water maze task compared to NBM-lesioned rats receiving vehicle infusion and untreated rats with NBM lesions. These studies indicate that the decrease in cortical ChAT activity is likely to be responsible for the observed acquisition deficit and that pharmacological manipulations can be successfully used to improve behavior following NBM lesions.

Animals↗
PubMed1989

Multisite recording of brain field potentials and unit activity in freely moving rats.

A technique has been developed to record from 16 different brain sites of the freely moving rat using subminiature MOSFET preamplifiers. The high input impedance, small size, durability and light weight of the amplifiers and connecting cable allows high quality multisite recording of field potentials and unit activity. In addition, a movable headstage for positioning multiple microelectrodes is described. The compact recording system permits one to construct neocortical EEG maps, instant depth profiles of evoked and spontaneous field data, and to study neuronal synchrony of distant cell populations.

Action Potentials↗
PubMed1989

Continuous physostigmine infusion in rats with excitotoxic lesions of the nucleus basalis magnocellularis: effects on performance in the water maze task and cortical cholinergic markers.

Acute peripheral administration of physostigmine inhibits cortical acetylcholinesterase (AChE) for about 1 hr in the rat and improves performance on learning and memory paradigms after excitotoxic lesions of the nucleus basalis magnocellularis (NBM) in rats. This study examined the effects of continuous systemic infusion of physostigmine using osmotic minipumps. One week of continuous physostigmine infusion in normal animals inhibited cortical AChE activity in a dose-dependent manner. Doses causing near maximal (0.06 mg/kg/hr) and ED50 (0.0075 mg/kg/hr) inhibition of cortical AChE activity were used to determine the effects of continuous physostigmine administration on spatial learning in the water maze in rats with bilateral ibotenic acid lesions of the NBM. Physostigmine had no effect on the acquisition of the maze task but prevented the retention deficit measured in untreated NBM-lesioned rats. Physostigmine treatment also improved the search strategy during the spatial probe trial compared to the untreated NBM-lesioned rats. The two doses of physostigmine examined did not produce differential responses on behavioral measures. Although NBM lesions significantly depleted cortical AChE activity, physostigmine treatment reduced the activity further in a dose-dependent manner. Whereas neither the lesion nor the low dose of physostigmine altered cortical receptor binding, the higher dose of physostigmine significantly down-regulated cortical muscarinic receptor binding by 28%. These data demonstrate that enhancement of acetylcholine neurotransmission can improve memory loss and spatial strategy associated with excitotoxic NBM lesions.

Acetylcholinesterase↗
PubMed1988

Physostigmine improves water maze performance following nucleus basalis magnocellularis lesions in rats.

Bilateral excitotoxic lesions of the nucleus basalis magnocellularis in rats were used along with testing in the water maze task to assess whether inhibition of acetylcholinesterase with physostigmine would reverse the lesion-induced impairment. Rats were lesioned bilaterally in stages using ibotenic acid and then behaviorally tested 3 weeks after surgery. Lesioned animals were administered one of three doses of physostigmine (0.06, 0.19, or 0.32 mg/kg) or vehicle solution 15 min prior to water maze testing. Sham lesioned animals injected with vehicle solution served as an untreated control group. Animals were tested for 5 consecutive days followed by 2 days off and then tested for 5 additional days. The rats were then sacrificed and their frontal cortex was assayed for choline acetyltransferase. The nucleus basalis magnocellularis lesion caused approximately a 27% depletion of choline acetyltransferase in the frontal cortex of these animals. The lesion also impaired the performance of the rats given vehicle solution as compared to untreated controls. Two doses (0.06 and 0.19 mg/kg) of physostigmine improved performance relative to lesioned controls. The lower dose, 0.06 mg/kg, improved performance more than the 0.19 mg/kg dose of physostigmine. The highest dose of physostigmine impaired water maze performance relative to lesioned controls. These data are discussed in relation to the cholinergic hypothesis of Alzheimer's disease and the potential therapeutic use of physostigmine.

Acetylcholinesterase↗
PubMed1987

Alteration of calmodulin distribution does not accompany dopaminergic supersensitization of the mouse striatum.

Membrane-bound calmodulin increases following dopaminergic supersensitization of the rat striatum. To assess the generality of this relationship, mice were treated with two different supersensitization paradigms. Calmodulin levels and subcellular distribution were determined by radioimmunoassay. Chronic haloperidol treatment increased striatal D2 dopamine receptor density by 25% but had no effect on membrane-bound calmodulin levels. Similarly, 6-hydroxy-dopamine (6-OHDA) lesions depleted striatal dopamine content greater than 95% without affecting membrane-bound calmodulin. In contrast, soluble calmodulin levels decreased by 15% in the 6-OHDA-lesioned striatum, suggesting that soluble calmodulin is enriched in presynaptic dopaminergic terminals. We conclude that dopaminergic supersensitization can occur in the mouse striatum in the absence of any change in calmodulin distribution.

Animals↗
PubMed1985

Quantification of lesion-induced dopaminergic supersensitivity using the rotational model in the mouse.

A dual lesion technique was used to determine the degree of supersensitivity resulting from nigrostriatal lesions in C57BL/6J mice. Internal capsule lesions encroaching on globus pallidus resulted in reliable ipsilateral rotation both to apomorphine and amphetamine. Dose-response curves to apomorphine were determined before and 21 days after 6-hydroxydopamine lesion of the contralateral nigrostriatal pathway. A 31.5-fold shift to the left was observed following the nigrostriatal lesion, with no change in slope. The extent and placement of the internal capsule lesion, as well as the magnitude of supersensitization correspond closely to those previously reported in the rat.

Animals↗
PubMedDate not supplied

Hypotensive anesthesia and autotransfusion in spinal surgery.

Sixty-eight (68) spinal operations performed under normotensive anesthesia were compared with 77 procedures performed under controlled hypotensive anesthesia. Procedures reviewed included Harrington instrumentation and fusion, dorsal arch resection, laminectomies and other spinal fusions. Intraoperative and postoperative blood loss and blood replacement were found to be reduced by approximately 50% in the group undergoing controlled hypotensive anesthesia for each procedure reviewed. This reduction in blood loss was achieved with only a moderate reduction in blood pressure (20 mm Hg systolic). Reduction in systolic blood pressure of greater than 20 mm was not associated with greater reduction in blood loss. Deliberate hypotension was coupled with hemodilution, lowering the hematocrit to 28% to 30% in order to increase cardiac output, increase tissue perfusion and decrease venous stasis. Autotransfusion has further reduced the need for homologous transfusion such that the combined techniques of hypotension and autotransfusion can eliminate the need for homologous blood transfusion in all but the most unusual cases.

Blood Pressure↗