Biomedical subjects

A M Lin

Publications and source records attributed to A M Lin.

36 records · Page 2Linked to original sources

PubMed1994

Ethanol-induced depressions of cerebellar Purkinje neurons are potentiated by beta-adrenergic mechanisms in rat brain.

Electrophysiological studies indicate that EtOH decreases the firing rate of cerebellar Purkinje neurons in vivo and in vitro through a GABAA mechanism. These neurons receive a prominent noradrenergic input from the locus coeruleus. Stimulation of the locus coeruleus or local application of beta-adrenergic agonists potentiates Purkinje neuron responses to GABA and sensitizes GABA responses to the potentiative effects of EtOH. In the present study, we found that the modulatory influences of the beta-adrenergic agonist isoproterenol potentiated EtOH-induced depressions of Purkinje neuron firing. This isoproterenol interaction with EtOH was antagonized by the beta-adrenergic antagonist timolol. We found evidence that endogenous catecholamines can cause this effect as well. Timolol antagonized EtOH-induced depressions on 20% of the neurons studied. This was the same frequency as that previously found for EtOH-induced potentiations of GABA depressions in this brain area. These data suggest that the Purkinje neurons showing this interaction receive spontaneously active catecholamine inputs that sensitize the GABA effects to the potentiative effects of ethanol. Consistent with this hypothesis, we also found that timolol antagonized this GABA/EtOH interaction. Taken together, these results are consistent with the hypothesis that EtOH-induced depressions of Purkinje neurons involved endogenous GABA actions that may be regulated by beta-adrenergic mechanisms.

Animals↗

PubMed1993

Ethanol inhibits the uptake of exogenous norepinephrine from the extracellular space of the rat cerebellum.

Rapid chronoamperometric recordings using nafion-coated carbon fiber electrodes coupled with pressure-ejection of drugs were used to investigate the effects of ethanol on norepinephrine (NE)-containing nerve terminals in the urethane-anesthetized Fischer 344 rat. Local application of ethanol from a double-barrel micropipette did not produce detectable changes in extracellular levels of NE in the rat cerebellar cortex. However, when ethanol was applied prior to local application of NE, it was seen to inhibit the uptake of NE from the extracellular space. These results were compared to the effects seen from the local application of a known high-affinity uptake inhibitor, nomifensine. Nomifensine was found to inhibit the extracellular uptake of NE in rat cerebeller cortex similar to ethanol. Our results support the hypothesis that one effect of ethanol on the noradrenergic system of the rat cerebellum is an alteration in the uptake of NE into NE-containing nerve endings. In addition, the present data concerning ethanol-induced inhibition of NE clearance or uptake support our previous electrophysiological studies in which we found that ethanol can potentiate the modulatory effects of beta-agonists on GABA responses of cerebellar Purkinje neurons.

Animals↗

PubMed1993

The effects of ethanol on gamma-aminobutyric acid-induced depressions of cerebellar Purkinje neurons: influence of beta adrenergic receptor action in young and aged Fischer 344 rats.

We reported previously that both the systemic administration and the local application of ethanol potentiated gamma-aminobutyric acid (GABA)-induced depressions of cerebellar Purkinje neurons if the GABA responses were concomitantly facilitated (positively modulated) by a beta adrenergic agonist, such as isoproterenol (ISO). In the present study we investigated the influence of aging on the beta adrenergic sensitization of GABA responses in young and aged Fischer 344 (F344) rats which exhibit age-related deficits in beta adrenergic receptor functions in the cerebellum. We found that the efficacy of ISO to modulate GABA responses was less in aged F344 rats vs. young F344 rats and that ethanol potentiated further the ISO-facilitated GABA responses of only 15% of the cerebellar Purkinje neurons recorded from aged F344 rats compared to 56% of the neurons from young F344 rats. Furthermore, in aged F344 rats, local applications of ISO frequently attenuated (negatively modulated) GABA responses of cerebellar Purkinje neurons and ethanol decreased further these attenuated GABA responses. Similar interactions were only observed infrequently from young F344 rats. In addition, these data suggest that age-related changes in the function of beta adrenergic mechanisms in the cerebellum are reflected not only in the decreased frequency of neurons exhibiting ethanol potentiation of ISO-modulated GABA effects but also in the observation that ethanol reduced GABA responses even in the presence of beta adrenergic receptor stimulations. This latter ethanol effect may also involve a beta adrenergic mechanism.

Aging↗

PubMed1993

Sensitization of gamma-aminobutyric acid-induced depressions of cerebellar Purkinje neurons to the potentiative effects of ethanol by beta adrenergic mechanisms in rat brain.

We previously reported that both systemic administration and brief local application of ethanol potentiated gamma-aminobutyric acid (GABA)-induced depressions of cerebellar Purkinje neurons when the GABA responses were concomitantly facilitated (modulated) by catecholaminergic agonists. In the present study, we further investigated the effects of prolonged local applications of ethanol, which more closely mimic the systemic application of ethanol, and we characterized the pharmacological specificity of the catecholaminergic interaction with these ethanol effects. As has been previously observed, iontophoretic applications of isoproterenol (ISO), a beta adrenergic agonist, facilitated GABA-induced depressions of cerebellar Purkinje neurons. The prolonged local application of ethanol produced a long-lasting potentiation of the ISO-modulated GABA responses that was similar in duration to that caused by systemic ethanol administration. The ethanol-induced augmentation of the ISO-modulated GABA responses was diminished both by terminating the beta adrenergic agonist application as well as by administering the beta adrenergic antagonist timolol. The alpha adrenergic agonist phenylephrine, on the other hand, either attenuated or had no effects on the GABA-induced depressions of cerebellar Purkinje neurons, and a subsequent application of ethanol did not potentiate GABA responses in the presence of phenylephrine. We conclude that prolonged local application of ethanol mimics the interaction of systemic ethanol with GABA-induced depressions of cerebellar Purkinje neurons. Furthermore, the catecholaminergic sensitization of GABA responses to these potentiative effects of ethanol is mediated by a beta adrenergic mechanism.

Animals↗

PubMed1992

Afferent and efferent connections of the paramedian reticular nucleus in the brain stem of cats.

Anatomical connections of the paramedian reticular nucleus (PRN) of the caudal medulla were investigated using a bi-directional tracer, horseradish peroxidase (HRP). The followings were observed when the tracer was microinjected to PRN: A. Both labelled neurons and terminals were found in the areas of the mesencephalic cardioinhibitory mechanism (CIM), the gigantocellular reticular nucleus (GRN), the ambiguus nucleus (AN) and the contralateral PRN. B. Only labelled terminals were demonstrated in the area of the nucleus of solitary tract (NTS) and the intermedial lateral cell column (IML) of the spinal cord. C. Only retrogradely labelled neurons were observed in the areas of the dorsal and dorsomedial medulla (DM) and ventrolateral medulla (VLM). A few labelled neurons were observed in the periaqueductal gray, the cuneiform nucleus and superior colliculus of the mesencephalon as well as the alamina spinal trigeminal nucleus. When HRP was applied to the CIM, GRN or AN structures, respectively, both labelled cells and terminals were found in the PRN area. HRP injection in the VLM showed only labelled terminals in the PRN. However, injection of HRP to DM showed neither labelling neurons nor terminals in PRN. Results suggest that PRN projects to the pressor area of DM/NTS and IML through which PRN could exert its inhibitory functions on the sympathetic pressor actions. In addition, PRN may suppress the vagal bradycardiac action through its reciprocal connections with CIM, GRN and AN. No lateralization in the PRN pathway was evident.

Afferent Pathways↗

PubMed1991

Ethanol potentiation of GABA-induced electrophysiological responses in cerebellum: requirement for catecholamine modulation.

In this study, we confirmed that microiontophoretically applied norepinephrine (NE) and isoproterenol potentiate the depressant effects of locally-applied gamma-aminobutyric acid (GABA) on cerebellar Purkinje neurons of anesthetized rats. Although ethanol (EtOH) does not reliably or efficaciously potentiate GABA-induced depressions of neuronal activity, we found that systemic or locally-applied EtOH does markedly potentiate GABA-induced inhibitions of Purkinje neuron firing rate if that response is concomitantly modulated by NE or isoproterenol. This study suggests that the EtOH sensitivity of the GABA mechanism of electrophysiological responses in the cerebellar cortex is regulated by the neuromodulatory effect of beta-adrenergic receptor activation.

Action Potentials↗

PubMed1991

Sympathoadrenal excitation and inhibition by lower brainstem stimulation in cats.

Effects of stimulation of brainstem sites on hemodynamics and plasma catecholamine levels were assessed in cats under chloralose-urethane anesthesia. Pressor areas of the dorsal medulla (DM) and ventrolateral medulla (VLM) and the depressor area of the paramedian reticular nucleus (PRN) were stimulated electrically using a monopolar electrode, or chemically using sodium glutamate microinjection. Plasma levels of norepinephrine (NE) and epinephrine (EPI) were measured in caval blood above the adrenal veins. Electrical stimulation of the DM and VLM produced increases in blood pressure and in plasma NE and EPI levels that were enhanced after acute vagotomies. The NE and EPI responses were attenuated after acute, bilateral adrenalectomies, confirming augmented adrenomedullary secretion, whereas the pressor responses were intact. Injection of sodium glutamate into the same pressor regions of the DM or VLM also produced pressor responses and elevated plasma catecholamine levels, indicating that the responses resulted from activation of neuronal perikarya. Stimulation of the PRN attenuated pressor and catecholamine responses during stimulation of the DM and VLM. The results indicate that pressor responses during stimulation of the DM and VLM are due at least partly to activation of perikarya in these regions, are associated with but not dependent on adrenomedullary activation, and are enhanced after vagotomy; and that neurons of the PRN exert inhibitory modulation of the pressor and adrenomedullary responses during stimulation of VLM and DM.

Adrenal Glands↗

PubMed1991

Responses of neurons in paramedian reticular nucleus to chemical stimulations and alteration of blood pressure in rats.

Previous studies have shown that paramedian reticular nucleus (PRN) possessed sympathetic and parasympathetic inhibitions on autonomic nervous system. In the present study, the cardiovascular reactions of PRN by locally-applied DL-homocysteic acid (DLH), acetylcholine (ACh), monoamines and electrophysiological properties of PRN neurons responding to intravenous injection of ACh and NE were studied in adult Sprague-Dawley rats. In PRN, electrical stimulation caused hypotension and mild bradycardia while microinjection of DLH, which excites only cell body of the neurons but not passing fibers, evoked similar responses. Furthermore, direct application of ACh, norepinephrine (NE) or serotonin (5-HT) in PRN also produced hypotension, suggesting that these putative neurotransmitters may be involved in the cardiovascular responses in PRN. The electrophysiological properties of PRN neurons were studied: Neurons in PRN could be categorized into three types according to their neuronal activities in response to the changes of systemic arterial blood pressure (SAP) by ACh or NE given intravenously. Type I neurons (25/69) were activated in the same direction of SAP changes. Type II neurons (17/69) responded opposite to the direction of SAP changes. Type III neurons (27/69) responded inconsistently to the changes of SAP. All the three types of neurons were excited by locally-applied DLH and possessed a similar unfiltered action potential duration of greater than 0.5 msec.

Acetylcholine↗

PubMed1991

Afferent and efferent connections of the mesencephalic cardioinhibitory area (CIM) in the cat.

The afferent and efferent connections between the cardioinhibitory area in the midbrain tegmental field (CIM) and brain stem structures related to cardiovascular integration in cats were investigated by horseradish peroxidase (HRP) for both cell origins and axonal terminations and by chemical (kainic acid) lesion for topographic pathways. Retrogradely labeled neurons were observed in the gigantocellular reticular nucleus (GRN), the pontine reticular nucleus of the pons (PON), the ambiguus nucleus (AN) and the paramedian reticular nucleus (PRN). A few neurons were also labeled in the following structures i.e., ventrolateral medulla (VLM), dorsomedial medulla (DMM), dorsomotor nucleus of the vagus nerve (DMV) and nucleus of solitary tract (NTS). Anterograde HRP labeled terminals were found surrounding the cell bodies of the aforementioned structures. They were most abundant in VLM, DMM, DMV, NTS, moderate in GRN, PRN and AN, but only scanty in hypothalamus. The fiber pathway of CIM neurons was also traced by degenerating fibers consequent to kainic acid lesion and by means of silver stain. Degenerating fiber bundle was found primarily projecting through the medial portion of the mesencephalic pontine structures. As the bundle reached the medulla oblongata, it bifurcated into a dorsal and a ventral tracts on its course. The dorsal tract was primarily coursing through the dorsomedial area, including DMM, NTS and DMV, and the ventral tract was mainly passing VLM, AN and inferior olivary nucleus (ION) areas. The present findings suggest that neurons in the CIM may receive inputs from various cardiovascular-related structures and make output bilaterally to some of pontine and medullary structures to modulate cardiovascular functions. Based on the anatomical findings, the profound bradycardia produced by CIM stimulation may be mediated through the following mechanisms: A. Direct activation of vagal preganglionic neurons in DMV, AN and ION. B. Indirect activation of neurons in GRN for vagal activation and of neurons in PRN for sympathetic inhibition.

Afferent Pathways↗

PubMed1989

Homocysteic acid elicits pressor responses from ventrolateral medulla and dorsomedial medulla.

In rats and cats anesthetized with alpha-chloralose and urethane, the pressor response and its relative reactivity were studied following microinjection of dl-homocysteic acid (DLH, 2 nmol in 40 nl of saline) into the dorsomedial medulla (DM) or the ventrolateral medulla (VLM). DLH, which excites only cell bodies of neurons but not fibers of passage, consistently produced pressor responses in DM and VLM in both cats and rats. The pressor effects elicited from VLM were more pronounced than those from DM. In cats, the most active areas for DLH were found in the rostral and midmedulla; the pons and caudal medulla were less active. The pressor responses from DM and VLM were augmented following bilateral vagotomy, persisted after sectioning of the carotid sinus and aortic depressor nerves, and after cauterization of the carotid bodies with phenol. The response induced by DLH was more apparent from VLM than that from DM. These pressor effects were evoked directly by activation of neurons in these two regions, and were not necessarily related to any homocysteate blockade of baroreceptor and/or chemoreceptor reflexes. These results suggest that in the medulla there reside at least two discrete pressor areas, DM and VLM containing neuronal perikarya.

Animals↗

PubMed1989

Contribution between dorsal and ventrolateral regions of medulla oblongata in vasomotor function of cats.

In cats anesthetized with alpha-chloralose and urethane, the medulla oblongata was explored with electrical and/or chemical stimulation for vasopressor actions. Chemical stimulation included semimicroinjection of sodium glutamate or microinjection of dl-homocysteic acid (DLH). The dorsal (DM), particularly its dorsomedial (DMM) portion, and the ventrolateral (VLM) regions were found to be most sensitive to both electrical and chemical stimulation. In between these two regions there was an area in the ventral portion of the gigantocellular and the parvocellular reticular nuclei that was sensitive to electrical and somewhat sensitive also to chemical stimulation. The responses to chemical stimulation indicate the existence of perikarya in these three areas for vasopressor actions. The most active response of VLM followed microinjection of DLH into the region of nu. paragigantocellularis lateralis (PGL) and subretrofacial nu. These responses were about 30% greater than those from DM where the most active area was found in the DMM region including the nu. and tractus solitarius. When an extensive area of VLM was lesioned bilaterally with kainic acid (KA, 1 micrograms/100 nl), the resting systemic arterial blood pressure (SAP) fell 42% and the pressor response on DM stimulation fell by more than 80%. In contrast, after similar KA bilateral destruction of DM the resting SAP fell 38% and the pressor responses from 67%. When only a limited area in the PGL/subretrofacial nu. of the rostral VLM (3-4 pressor sites, 1 mm apart) on one side was lesioned, the resting SAP remained unaltered while the pressor response on the ipsilateral DMM decreased 76%. On the other hand, when a similar smaller KA lesion (3-4 sites) was made in the DMM, although the resting SAP did not change, the pressor response on stimulation of the ipsilateral rostral VLM decreased 28%. Further lesioning of the contralateral DMM then decreased the rostral VLM pressor response 62% without much alternation in the resting SAP. Results of the present experiments are in accordance with our previous results that neuronal perikarya for vasopressor action exist not only in VLM but also in DM (18,34) with the function of VLM slightly predominant over DM. It seems highly possible that reciprocal innervation exists between DM and VLM, at least between DMM and the PGL/subretrofacial nu. region.

Animals↗

PubMed1988

Correlated effects of guanabenz on single-neuron activity in the nucleus reticularis gigantocellularis, systemic arterial pressure and heart rate in the rat.

The simultaneous effects of guanabenz on the activity of single-neurons in the nucleus reticularis gigantocellularis of the medulla oblongata, systemic arterial pressure and heart rate were assessed in Sprague-Dawley rats, anesthetized with pentobarbital sodium (40 mg/kg, i.p.). Of the 35 arterial pressure-related neurons (neurons that temporally altered their spike rhythm subsequent to fluctuations in arterial pressure) which were evaluated in this reticular nucleus, 32 changed their discharge frequencies that exhibited a degree and time-course parallel to the hypotension promoted by the amino-guanidine compound (5, 10 or 20 micrograms/kg, i.v.). More importantly, these alterations neuronal activity preceded the occurrence of the induced vasodepression, signifying a causative relationship between the two events. Four of the 5 non-arterial pressure-related neurons in the gigantocellular reticular nucleus, on the other hand, manifested no basic modification in their spike frequencies in relation to the hypotension induced by guanabenz. These observations provided further support for the idea that the nucleus reticularis gigantocellularis participates actively in the cardiovascular suppressive actions of the aminoguanidine compound.

Action Potentials↗

PubMed1988

Existence of a powerful inhibitory mechanism in the medial region of caudal medulla--with special reference to the paramedian reticular nucleus.

Inhibitory actions of the medial trigon of the caudal medulla (ITM) with special reference to the paramedian reticular nucleus (PRN) were explored in cats under chloralose (40 mg/kg) and urethane (400 mg/kg) anesthesia. Stimulation with square wave pulses (80 Hz, 1 msec, 100-200 microA) produced a reduction of mean systemic arterial blood pressure (MSAP) of 15-90 mmHg, and change in heart rate (HR) that varied from mild increase of 15 to reduction of 85 beats/min. These responses were not affected by mid-collicular decerebration nor by bilateral vagotomy. Destruction of PRN did not change the resting MSAP, HR or baroreceptor reflex responses. Stimulation of PRN suppressed the sympathetic pressor and cardioacceleratory and the vagal bradycardia responses resulting from activating cardiovascular (CV) regulatory mechanisms in the hypothalamus, midbrain and medulla, or from activating the somatic or the baroreceptive afferents. Activation of the PRN suppressed the MSAP-increase produced by direct stimulation of the stellate or celiac ganglion. PRN stimulation could eliminate the pronounced CV reactions consequent either to asphyxial anoxia during occlusion of the trachea or to cerebral ischemia following occlusion of vertebral and carotid arteries. Furthermore, PRN activation could stop the general convulsion of the animal induced by picrotoxin, 4 mg/kg, IV. Our findings suggest that in the trigon area especially in the PRN, there resides an independent mechanism which exerts very powerful and broad inhibitory actions on the autonomic as well as somatic nervous system.

Afferent Pathways↗

PubMed1988

Paramedian reticular nucleus--sympathetic inhibition in spontaneously hypertensive rats.

The cardiovascular reactivity of various areas in the medulla related to sympathetic or parasympathetic activation, or to sympathetic inhibition, was compared in spontaneously hypertensive rats (SHR) and in normotensive rats Wistar-Kyoto (WKY) or Sprague-Dawley (SD). In SHR, which has an elevated resting systemic arterial blood pressure (SAP), the sympathetic pressor responses elicited from electrical stimulation of the dorsomedial medulla (DMM), parvocellular lateral nucleus (PVC) or ventrolateral medulla (VLM) were more profound than those in WKY and SD. The depressor and bradycardia responses elicited from electrical stimulation of the paramedian reticular nucleus (PRN) (which exerts both sympathetic and parasympathetic inhibitions) or from the area of the solitary nucleus/dorsomotor nucleus of vagus (NTS/DMV) (where stimulation leads to both parasympathetic activation and sympathetic inhibition) were also more intensive in SHR than in WKY and SD. The elicited pressor and depressor responses, however, were not significantly different between WKY and SD. Our results are consistent with previous findings (15) that in SHR an increased sympathetic activity of the pressor areas of medulla contributes to the pathogenesis of hypertension. Sympathetic inhibition (PRN and NTS/DMV areas) and parasympathetic activation (NTS/DMV area) from these areas, however, may not be critically involved.

Animals↗

PubMed1988

Pressor responses from electrical or glutamate stimulations of the dorsal or ventrolateral medulla.

In rats, rabbits, and cats anesthetized with alpha-chloralose and urethan, responses of the pressor areas of the dorsal portion (DM) and ventrolateral portion (VLM) of medulla and pons were compared. Electrical stimulation (monopolar square-wave pulses) on monosodium glutamate solution (Glu, 100-200 nl, 1 M) was delivered through an electrode-needle tubing connected to a Hamilton syringe for semimicroinjection. In all three of these species, pressor responses were elicited from both DM and VLM by either Glu or electrical stimulation. The most active parts of DM were found in the dorsomedial reticular formation of the rostral medulla to mid-medulla. In the pons and caudal medulla, the Glu-induced response was mild, although the electrically induced response was marked. Application of kainic acid (KA) to either DM or VLM produced an initial pressor response but was followed by a reduction of the pressure rise on subsequent electrical stimulation. Glu, unlike electrical stimulation, excites neural perikarya, not fibers of passage. KA initially excites the neural perikarya before causing damage that spares axons. These results thus suggest that both DM and VLM contain neural perikarya that mediate pressor effects.

Animals↗

PubMed1988

Influence of rostral neural structures on the vasomotor functions of the medulla oblongata.

Chinese J. Physiol 31(2): 79-93, 1988. In cats, the resting systemic arterial blood pressure (SAP) which rises on electrical stimulation of the dorsal medulla (DM), ventrolateral medulla (VLM) and paramedian reticular nucleus (PRN) under anesthesia with 2% halothane in oxygen were compared with those 30 min after termination of the inhalation (with application of lidocaine on the surgical wound and i.v. gallamine 2 mg/kg). The resting SAP under halothane were significantly lowered and functions of the DM and VLM much depressed. The depressor response of PRN stimulation was converted to the pressor one after deprivation of halothane anesthesia. In animals under little anesthetic influence, midcollicular decerebration significantly lowered the resting SAP, but both DM and VLM pressor responses were not significantly changed. In addition, the decerebration significantly diminished the peak pressor effects on PRN stimulation. Findings suggest that rostral neuro-structures do exert tonic influence (both excitatory and inhibitory) on medulla vasomotor functions. This is quite different from the classical concept, first proposed by Dittmar and Owsjannikown (1870s) and still considered nowadays as truthful, that the neural structures rostral to the caudal one third of pons was not critical in maintaining the resting SAP.

Animals↗

PubMed1987

A cardioinhibitory area in the midbrain central tegmental field of cats.

A cardioinhibitory area in the central tegmental field of the midbrain (CIM) was studied in cats under chloralose-urethane anesthesia. Electrical and chemical (glutamate and DL-homocysteic acid) stimulations in this area produced marked bradycardia accompanied by mostly hypotension or minimal change in arterial pressure and by occasional hypertension particularly in the dorsal portion. CIM excitation potentiated the reflex bradycardia induced by IV phenylephrine, while bilateral electrolytic lesion of CIM neither changed the resting cardiovascular parameters nor the reflex bradycardia. The CIM bradycardia was not affected by supracollicular decerebration, but substantially reduced by unilateral vagotomy and completely eliminated by bilateral vagotomy. Destruction of the ambiguus nucleus (NA) and solitary and dorsal motor nuclei (NTS/DMV) abolished the bradycardia. Midline bisection at the midbrain-pontine level only slightly reduced the bradycardia while at the medullary level it was moderately attenuated. Electrolytic lesion of the cardioinhibitory area in gigantocellular reticular nucleus (GRN) abolished the bradycardia. These findings suggest that CIM is an independent mechanism which may send axons to GRN from which the axons may in turn synapse with the NTS/DMV complex and NA. Its final output may utilize both vagus nerves to modulate baroreceptor reflex in promoting bradycardia.

Animals↗

PubMedDate not supplied

Long-term treatment of male F344 rats with deprenyl: assessment of effects on longevity, behavior, and brain function.

L-Deprenyl (selegiline) was chronically administered to male Fischer 344 rats via their drinking water beginning at 54 weeks of age (estimated daily dose: 0.5 mg/kg/day). Beginning at 84 weeks of age, the rats were behaviorally evaluated using a sensorimotor battery, a motor-learning task, and the Morris water maze. At 118 weeks of age, cerebellar noradrenergic function was evaluated in the surviving rats using in vivo electrochemistry. The rats were then sacrificed to measure brain monoamine oxidase activity and perform quantitative autoradiography to evaluate the effect of chronic deprenyl treatment on beta-adrenergic receptors in the cerebellum, alpha 2-adrenergic receptors several brain regions, and D1 and D2 dopamine receptors in the striatum. Deprenyl treatment reduced brain monoamine oxidase B activity by 85%, but had no effect on brain monoamine oxidase A. A clear effect of chronic deprenyl treatment upon longevity was not observed. Several measures of CNS function were altered in the deprenyl-treated animals: 1) spatial learning in the Morris water maze was improved; 2) electrochemical signals recorded following local application of NE were reduced, and the responsiveness to the reuptake blocker nomifensine was enhanced, in the cerebellum; 3) beta-adrenergic receptor binding affinity was increased in the cerebellum; 4) alpha 2-adrenergic receptor density was increased in the inferior colliculus; and 5) striatal D1 dopamine receptor density was reduced but binding affinity was enhanced. In contrast, chronic deprenyl treatment did not cause changes in: 1) sensorimotor function, as evaluated by balance beam, inclined screen, or wire hang tasks; 2) motor learning; 3) alpha 2-adrenergic receptor density in any region examined except for the inferior colliculus, or binding affinity in any region examined; or 4) striatal D2 dopamine receptor number or affinity. Thus, long-term oral administration of deprenyl extended the functional life span of rats with respect to cognitive, but not motor, performance.

Animals↗