Biomedical subjects

R J Beninger

Publications and source records attributed to R J Beninger.

At least 19 recordsLinked to original sources

PubMed2006

Movement disorders: neurodevelopment and neurobehavioural expression.

Braak and co-workers have recently shown that movement disorders such as Parkinson's disease develop progressively over years with early neuronal losses in brainstem regions caudal to the substantia nigra. The relevance of this finding to notions of comorbidity between movement disorders and psychiatric symptoms was recognised at the recent meeting concerning, "Implications of Comorbidity for the Etiology and Treatment of Neuropsychiatric Disorders" held in Oct. 2005 in Mazagon, Spain. The identification of stages in the early development of neurodegenerative disorders appeared to unify multiple, diverse findings. These included: novel therapeutic innovations for Parkinson's disease, Alzheimer's disease and depression in the aged; the neurochemical ontogeny of drug-induced oral dyskinesias; the types of chemical agents abused in neuropsychiatric states; postnatal iron overload effects upon the functional and interactive role of dopaminergic and noradrenergic pathways that contribute to the expression of movement disorders; and the spectrum of motor symptoms expressed in schizophrenia and attention deficit hyperactivity disorder and the eventual treatment of these disorders. A continued focus on a number of neuropsychiatric diseases as progressive disorders may lead to further advances in understanding their etiology and in developing better therapeutics.

Animals↗

PubMed2006

Behavioural sensitization in addiction, schizophrenia, Parkinson's disease and dyskinesia.

Incentive learning takes place when dopaminergic neurons are activated, usually by rewards. As a result, previously neutral stimuli associated with reward acquire incentive salience and thus the ability to elicit approach or other responses in the future. Incentive learning is assumed to underlie psychostimulant-induced context-dependent sensitization that may play a prominent role in the development of addiction, in dyskinesia, and in amphetamine-induced psychosis. Assuming that these pathological states are due to the gradual process of sensitization, the effects of therapeutics might be manifested as a gradual desensitization. This assumption could explain the delay between onset of cellular effects of drugs (e.g., dopamine receptor blockade) and the improvement in symptoms (e.g., decreases in psychotic symptoms). Reduced dopamine activity results in behavioural changes that are opposite to psychostimulant-induced sensitization, i.e., rewarded behaviours decline in an extinction-like fashion despite the presence and consumption of rewards. We show here that also non reward-related behaviour, i.e., motor activity and catalepsy, follows the same rules: motility is not switched off by dopamine receptor blockade or by 6-hydroxydopamine lesions, but shows a test-to-test extinction-like decline. Thus, psychostimulant-induced sensitization and dopamine-deficiency induced decline of behaviour follows similar rules but in opposite directions.

Animals↗

PubMed2005

The dopamine D(3) receptor-preferring partial agonist BP 897 dose-dependently attenuates the expression of amphetamine-conditioned place preference in rats.

Previously we reported that systemic administration of the dopamine D3 receptor-preferring partial agonist BP 897 blocked the expression, but not the acquisition, of amphetamine-conditioned activity. This suggested the hypothesis that BP 897 would block the expression, but not the acquisition, of amphetamine-conditioned place preference (CPP). Thus, during preconditioning rats had access to two chambers connected by a tunnel for three 15-min sessions. During eight conditioning days with the tunnel blocked, one chamber was paired with drug administration for four 30-min sessions, alternating with pairing of the other chamber with saline administration. In a drug-free test session, time on the drug-paired side was compared to time spent there in preconditioning; a significant increase was defined as a place preference. Systemic amphetamine (2.0 mg/kg) or amphetamine+BP 897 (1.0, 2.0 mg/kg) during conditioning produced a significant place preference, while administration of BP 897 (1.0 or 2.0 but not 0.5 mg/kg) during the test blocked the amphetamine-CPP. There was no evidence that BP 897 produced a conditioned aversion. Results supported the hypothesis that BP 897 would block expression, but not acquisition, of amphetamine-CPP.

Amphetamines↗

PubMed2004

Gene-environment interplay in affect and dementia: emotional modulation of cognitive expression in personal outcomes.

A multitude of factors, that either singly, interactively, or sequentially influence the gene-environment interplay in affective and dementia states, include several phases of neurodevelopmental liability in both humans and laboratory animals. Genetic vulnerability for both affective disorders and dementia describes a scenario distinguished by progressive need for concern, particularly in view of the interplay between these areas of ill-health. The contribution of emotional and cognitive expression to personal outcomes, e.g., as a function of affective personality type, a state-dependent analysis of personality characteristics, appears to pervade both the individual's experience of social and physical environments and the performance of cognitive tasks. The role of the endocannabinoids in mental health may offer insights for the psychopharmacology of both cognition and affect. Maladaptive emotional reactions and a defective cognitive ability will contribution to unsatisfactory/maladaptive coping strategies, in turn, leading to further complications of an affective and dysfunctional nature, eventually with a clinical psychopathological outcome. These considerations impinge upon critical issues concerning predisposition and vulnerability. Classical eye-blink conditioning provides a highly established procedure for assessment of defective physiology in models of Alzheimer's dementia. In order to develop a consideration of the array of situations presenting the variation of outcome due to type of affective personality, the role of fear and anxiety and stress in affective states influencing cognition are examined and the critical role of brain circuits mediating emotions influencing cognitive outcomes is discussed.

Adolescent↗

PubMed2004

Gene-environment interplay in alcoholism and other substance abuse disorders: expressions of heritability and factors influencing vulnerability.

Factors that confer predisposition and vulnerability for alcoholism and other substance abuse disorders may be described usefully within the gene-environment interplay framework. Thus, it is postulated that heritability provides a major contribution not only to alcohol but also to other substances of abuse. Studies of evoked potential amplitude reduction have provided a highly suitable and testable method for the assessment of both environmentally-determined and heritable characteristics pertaining to substance use and dependence. The different personal attributes that may co-exist with parental influence or exist in a shared, monozygotic relationship contribute to the final expression of addiction. In this connection, it appears that personality disorders are highly prevalent co-morbid conditions among addicted individuals, and, this co-morbidity is likely to be accounted for by multiple complex etiological relationships, not least in adolescent individuals. Co-morbidity associated with deficient executive functioning may be observed too in alcohol-related aggressiveness and crimes of violence. The successful intervention into alcohol dependence and craving brought about by baclofen in both human and animal studies elucidates glutamatergic mechanisms in alcoholism whereas the role of the dopamine transporter, in conjunction with both the noradrenergic and serotonergic transporters, are implicated in cocaine dependence and craving. The role of the cannabinoids in ontogeny through an influence upon the expression of key genes for the development of neurotransmitter systems must be considered. Finally, the particular form of behaviour/characteristic outcome due to childhood circumstance may lie with biological, gene-based determinants, for example individual characteristics of monoamine oxidase (MAO) activity levels, thereby rendering simple predictive measures both redundant and misguiding.

Alcoholism↗

PubMed2003

Brain sites of movement disorder: genetic and environmental agents in neurodevelopmental perturbations.

In assessing and assimilating the neurodevelopmental basis of the so-called movement disorders it is probably useful to establish certain concepts that will modulate both the variation and selection of affliction, mechanisms-processes and diversity of disease states. Both genetic, developmental and degenerative aberrations are to be encompassed within such an approach, as well as all deviations from the necessary components of behaviour that are generally understood to incorporate "normal" functioning. In the present treatise, both conditions of hyperactivity/hypoactivity, akinesia and bradykinesia together with a constellation of other symptoms and syndromes are considered in conjunction with the neuropharmacological and brain morphological alterations that may or may not accompany them, e.g. following neonatal denervation. As a case in point, the neuroanatomical and neurochemical points of interaction in Attention Deficit and Hyperactivity disorder (ADHD) are examined with reference to both the perinatal metallic and organic environment and genetic backgrounds. The role of apoptosis, as opposed to necrosis, in cell death during brain development necessitates careful considerations of the current explosion of evidence for brain nerve growth factors, neurotrophins and cytokines, and the processes regulating their appearance, release and fate. Some of these processes may possess putative inherited characteristics, like alpha-synuclein, others may to greater or lesser extents be endogenous or semi-endogenous (in food), like the tetrahydroisoquinolines, others exogenous until inhaled or injested through environmental accident, like heavy metals, e.g. mercury. Another central concept of neurodevelopment is cellular plasticity, thereby underlining the essential involvement of glutamate systems and N-methyl-D-aspartate receptor configurations. Finally, an essential assimilation of brain development in disease must delineate the relative merits of inherited as opposed to environmental risks not only for the commonly-regarded movement disorders, like Parkinson's disease, Huntington's disease and epilepsy, but also for afflictions bearing strong elements of psychosocial tragedy, like ADHD, autism and Savantism.

Ataxia↗

PubMed2002

Neurosteroids and glutamate toxicity in fibroblasts expressing human NMDA receptors.

We characterized glutamate receptor-mediated toxicity in mouse fibroblasts expressing the human NR1a/2A or NR1a/2B NMDA receptor. After induction of NMDA receptors, cells in both lines died over a 24 h time period. This toxicity was associated with a progressive increase in the glutamate content of the media. Cell death could be prevented by including either the non-competitive NMDA receptor antagonist ketamine or the competitive antagonist D,L-AP5. Cells expressing NR1a/2A receptors were maximally protected by 0.5 mM D,L -AP-5, while those expressing NR1a/2B receptors required 2 mM D,L -AP-5 for maximal protection. The neurosteroid pregnenolone sulfate, which negatively modulates NMDA receptor function, partially protected fibroblasts containing NR1a/2A or NR1a/2B NMDA receptor constructs. However, the neurosteroid pregnenolone sulfate, which has been reported to act as a positive allosteric modulator of the NMDA receptor, had no effect on the toxicity caused by endogenous glutamate. Our results on cells expressing human NMDA receptors suggest that certain neurosteroids may protect against NMDA induced toxicity while having low neurotoxic liabilities of their own.

Journal Article↗

PubMed2001

Cognitive effects of neurotoxic lesions of the nucleus basalis magnocellularis in rats: differential roles for corticopetal versus amygdalopetal projections.

The cholinergic hypothesis states that cholinergic neurons of the basal forebrain nucleus basalis magnocellularis (nbm) that project to cortical and amygdalar targets play an important role in memory. Biochemical studies have shown that these target areas are differentially sensitive to different excitotoxins (e.g., ibotenate vs. quisqualate). This observation might explain the finding from many behavioural studies of memory that different excitotoxins affect memory differentially even though they produce about the same level of depletion of cholinergic markers in the cortex and similar cortical electrophysiological effects. Thus, the magnitude of mnemonic impairment might be related to the extent of damage to cholinergic projections to the amygdala more than to the extent of damage to corticopetal cholinergic projections. This explanation might similarly apply to the observation that the immunotoxin 192 IgG-saporin produces mild effects on memory when injected into the nbm. This is because it damages cholinergic neurons projecting to the cortex but not those projecting to the amygdala. Studies comparing the effects on memory of ibotenic acid vs. quisqualic acid lesions of the nbm are reviewed as are studies of the mnemonic effects of 192 IgG-saporin. Results support the cholinergic hypothesis and suggest that amygdalopetal cholinergic neurons of the nbm play an important role in the control of memory.

Journal Article↗

PubMed2001

Pimozide, like extinction, devalues stimuli associated with sucrose taking.

Conditioned stimuli (CS) can be devalued by exposure to those stimuli in the absence of primary reward. We tested the hypothesis that dopamine (DA) mediates the control of behavior by conditioned appetitive stimuli. Long-Evans rats were trained to respond for sucrose under a heterogeneous chain schedule in which seeking responses (lever press) turned on a houselight [variable interval (VI)-120 s]; taking responses (wheel turn or chain pull) in the presence of the houselight were reinforced [fixed ratio (FR)-1] by a sucrose pellet. When responding on this schedule was stable, the levers were retracted and subjects had access to the sucrose-taking manipulandum only. Sucrose-taking responses were either extinguished or reinforced under the influence of the DA antagonist, pimozide. Control groups were also reinforced for sucrose-taking responses but received no injection or a vehicle injection prior to each session. Responses of extinction and pimozide-treated groups declined over sessions. Sucrose-seeking responses were measured in a later test when subjects had no access to the sucrose-taking manipulandum or to the reinforcer. Both extinction and pimozide manipulations reduced seeking responses, relative to the respective control groups. Pimozide injections in the home cage had no effect. These data support the idea that DA mediates the conditioned reinforcing properties provided by access to the taking link of the chain.

Animals↗

PubMed2001

Hippocampal-prefrontocortical circuits: PKA inhibition in the prefrontal cortex impairs delayed nonmatching in the radial maze in rats.

Recent findings implicate the prefrontal cortex (PFC) and, in particular, frontocortical dopamine acting at D1-like receptors, in working memory. However, the mechanisms underlying this function of dopamine remain unknown. The present studies evaluated the hypothesis that dopamine contributes to working memory through its action on the 2nd messenger cyclic 3',5'-adenosine monophosphate (cAMP) and cAMP-dependent protein kinase (PKA). Thus, rats were trained to perform random foraging or delayed (30 min) nonmatching-to-position (delayed win-shift) tasks on the radial maze. With hippocampal output to the frontal cortex disconnected by injecting lidocaine (20 microg/0.5 microl) unilaterally into the ventral subiculum, contralateral frontocortical injections of lidocaine (20 microg/0.5 microl) or the D1-like dopamine receptor antagonist SCH 23390 (0.5 microg/0.5 microl) impaired delayed win-shift but not random foraging, replicating previous findings. In similarly disconnected rats, frontocortical injections of the PKA inhibitor Rp-cAMPS (5.0 and 10.0, but not 1.0, microg/0.5 microl) selectively impaired delayed nonmatching-to-position. Results suggest that activation of the cAMP-PKA pathway by dopamine acting at D1-like receptors in the frontal cortex is necessary for working memory.

Animals↗

PubMed2000

Excitotoxicity of quinolinic acid: modulation by endogenous antagonists.

Quinolinic acid (QUIN), a product of tryptophan metabolism by the kynurenine pathway, produces excitotoxicity by activation of NMDA receptors. Focal injections of QUIN can deplete the biochemical markers for dopaminergic, cholinergic, gabaergic, enkephalinergic and NADPH diaphorase neurons, which differ in their sensitivity to its neurotoxic action. This effect of QUIN differs from that of other NMDA receptor agonists in terms of its dependency on the afferent glutamatergic input and its sensitivity to the receptor antagonists. The enzymatic pathway yielding QUIN produces metabolites that inhibit QUIN-induced neurotoxicity. The most active of these metabolites, kynurenic acid (KYNA), blocks NMDA and non-NMDA receptor activity. Treatment with kynurenine hydroxylase and kynureinase inhibitors increases levels of endogenous KYNA in the brain and protects against QUIN-induced neurotoxicity. Other neuroprotective strategies involve reduction in QUIN synthesis from its immediate precursor, or endogenous synthesis of 7-chloro-kynurenic acid, a NMDA antagonist, from its halogenated precursor. Several other tryptophan metabolites--quinaldic acid, hydroxyquinaldic acid and picolinic acid--also inhibit excitotoxic damage but their presence in the brain is uncertain. Picolinic acid is of interest since it inhibits excitotoxic but not neuroexcitatory responses. The mechanism of its anti-excitotoxic action is unclear but might involve zinc chelation. Neurotoxic actions of QUIN are modulated by nitric oxide (NO). Treatment with inhibitors of NO synthase can augment QUIN toxicity in some models of excitotoxicity suggesting a neuroprotective potential of endogenous NO. In recent studies, certain nitroso compounds which could be NO donors, have been reported to reduce the NMDA receptor-mediated neurotoxicity. The existence of endogenous compounds which inhibit excitotoxicity provides a basis for future development of novel and effective neuroprotectants.

Journal Article↗

PubMed2000

Neurosteroids and reward: allopregnanolone produces a conditioned place aversion in rats.

The neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone) has been reported to have rewarding properties in mice tested for place conditioning. Another study found that allopregnanolone reduced dopamine (DA) output in the nucleus accumbens (NAc) of rats. As many rewarding stimuli increase accumbens DA, these results may appear contradictory. Thus, the present study examined the rewarding properties of allopregnanolone in rats tested for place conditioning using an unbiased conditioning procedure. In control studies, a place preference was observed following conditioning with intraperitoneal (2.0 mg/kg) or intracerebroventricular (i.c.v.) (100 microg/0.5 microl) amphetamine. Conditioning with i.c.v. allopregnanolone produced a significant aversion at a dose of 5.0 microg (in 5.0 microl) and a near aversion at 25.0 microg (in 8.3 microl); doses of 0 microg (i.e., vehicle alone, in 10 microl) or 30.0 microg (in 10 microl) produced little effect on place preference. During conditioning, locomotor activity was stimulated by amphetamine using either route of administration, but allopregnanolone had no significant main effect on locomotor activity. Thus, there was a dissociation between the effects of drugs on locomotor activity vs. place conditioning. Results show that i.c.v. amphetamine produces a place preference, whereas allopregnanolone produces either no effect or an aversion, depending on the dose.

Amphetamine↗

PubMed2000

Turning in rats following intraaccumbens shell injections of amphetamine or eticlopride.

In recent years there has been interest in possible differential behavioral functions of the core and shell subregions of the nucleus accumbens. The present study compared the effects of accumbens core and shell injections of (+)-amphetamine on turning behavior in rats; the turning effects of the selective D2 antagonist (-)-eticlopride injected into the shell were also tested. Rats (n = 28) were implanted unilaterally with guide cannulae and subsequently tested for turning in seven 20-min sessions. Amphetamine (10.0 and 20.0 microg but not 5.0 microg/ 0.5 microl) elicited contralateral turning following injection into the shell, while the same doses into the core had no effect. In animals given systemic amphetamine (2.0 mg/kg), eticlopride (10.0 but not 1.0 or 0.1 microg/0.5 microl) injected into the shell region of the accumbens produced ipsilateral turning. These results suggest that the accumbens shell, but not the core, is a critical site for turning behavior.

Amphetamine↗

PubMed2000

Conditioned locomotion in rats following amphetamine infusion into the nucleus accumbens: blockade by coincident inhibition of protein kinase A.

Recent studies demonstrate a role for cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) in the nucleus accumbens (NAc) in reward-related learning. To clarify this role, we assessed the effect of PKA inhibition on the unconditioned and conditioned locomotor activating properties of intra-NAc amphetamine. Rats underwent three 60 min conditioning sessions, pairing a test environment with bilateral co-infusions of amphetamine (25 microg/side) and the PKA inhibitor Rp-adenosine 3',5'-cyclic monophosphothioate triethylamine (Rp-cAMPS) (0, 2.5, 250, 500 ng, 1, 10 or 20 microg/side). Two additional groups - receiving amphetamine explicitly unpaired with the environment or saline/environment pairings - served as controls. In a subsequent drug-free 60 min session, animals that received amphetamine/environment pairings demonstrated conditioned locomotion relative to controls. Rp-cAMPS co-treatment during pairing sessions differentially affected conditioned and unconditioned locomotor activation. Amphetamine-induced unconditioned activity was significantly enhanced by 500 ng and 1 microg Rp-cAMPS, locomotor sensitization was enhanced by 250 ng-1 microg Rp-cAMPS, and conditioned activity was attenuated by 1 microg Rp-cAMPS and blocked by 10 and 20 microg Rp-cAMPS. Thus, unconditioned activity and locomotor sensitization were enhanced at doses (250 ng-1 microg) that did not affect or attenuated conditioned activity, while conditioned activity was reduced or blocked at doses (1-20 microg) that enhanced or did not affect overall unconditioned activity. These results demonstrate that the activation of PKA plays a critical role in the process by which properties of drugs become associated with environmental stimuli.

Amphetamine↗

PubMed2000

The effects of amphetamine and raclopride on food transport: possible relation to defensive behavior in rats.

Recent work has shown that transport of food items from open, exposed food sources to a covered shelter is reduced by drugs thought to have anxiolytic properties in rodents and humans. We studied the effects of amphetamine and the dopamine D2/3-receptor antagonist, raclopride, in this test of food transport that pits immediate food consumption against exposure in an open space. Rats traveled from a home cage along an elevated beam to obtain single food items of varying sizes located at one of 12 distances from the home cage. Large food items and items located close to the home cage were carried back and consumed inside the cage. Small items and items located farther from the cage were eaten immediately at the food source while sitting on the beam. Amphetamine sulfate (0.001-2.0 mg/kg, i.p.) decreased eating on the beam and increased carrying of food items to the home cage. Raclopride (0.005-0.2 mg/kg, i.p.) tended to reduce carrying of food to the home cage, but 0.05 mg/kg raclopride did not block the increase in food carrying seen with amphetamine treatment (2 mg/kg). The increased food carrying seen with amphetamine is opposite to the effect produced by anxiolytic drugs, raising the possibility that amphetamine promotes carrying by increasing defense or 'anxiety'. Consistent with this hypothesis, amphetamine (2 mg/kg; the maximally effective dose in the food-carrying experiment) decreased open-arm exploration in the elevated plus-maze, considered to be an anxiogenic effect. These results indicate that stimulation of monoaminergic neurotransmission increases food transport from exposed food sources to a shelter; D2/3-receptor blockade tends to reduce it. The food-carrying test provides a rich, ethologically valid paradigm to assess the effects of psychoactive drugs on species-specific, defensive behaviors in rodents.

Amphetamine↗

PubMed2000

International Behavioral Neuroscience Society - Ninth meeting. Neurochemistry of feeding.

The neurochemistry of feeding was a highlight of this meeting. A number of peptides are now known to participate in the control of nutrient balance, and many of them featured in the meeting, including the feeding suppressors alpha-melanocyte-stimulating hormone, leptin and corticotrophin releasing hormone, and the orexigenic agents, melanin-concentrating hormone, Agouti-related peptide, orexin A and neuropeptide Y. Other substances that play a role in feeding are amylin and its antagonist, AC-187, histamine, dopamine, serotonin, opiates, galanin and CART peptides. The hypothalamic and extrahypothalamic localization of these feedingrelated substances and their interactions with one another, and other brain regions, are beginning to be understood. Another symposium focused on sigma receptor ligands, such as (+)-pentazocine, PRE-084, the neurosteroid pregnanolone sulfate, NE-100, igmesine (JO-1784) and BD-1008 and related compounds. Results showed that sigma ligands may affect Ca(2+) signaling via two modes of action, one being at the endoplasmic reticulum and the other at the plasma membrane. Sigma receptors have been implicated in learning and memory, and may play a role in anxiety and depression.

Journal Article↗

PubMed1999

Quinolinic acid lesion of the nigrostriatal pathway: effect on turning behaviour and protection by elevation of endogenous kynurenic acid in Rattus norvegicus.

Endogenous excitotoxins have been implicated in degeneration of nigral dopaminergic neurons in Parkinson's disease. It may be possible to reduce neurodegeneration by blocking the effects of these endogenous agents. The present study shows that contralateral turning seen following quinolinic acid-induced lesions of the nigrostriatal dopaminergic pathway was reversed by a treatment that increased brain levels of kynurenic acid, an endogenous excitatory amino acid antagonist. The treatment consisted of nicotinylalanine (5.6 nmol/5 microl i.c.v.), an inhibitor of kynureninase and kynurenine hydroxylase plus the precursor kynurenine (450 mg/kg i.p.) plus probenencid (200 mg/kg i.p.), an inhibitor of organic acid transport. Thus, neuroprotection by increasing brain kynurenic acid in vivo may be useful in retarding cell loss in Parkinson's and other neurodegenerative diseases involving excitotoxicity.

Alanine↗

PubMed1999

Modulation of quinolinic acid-induced depletion of striatal NADPH diaphorase and enkephalinergic neurons by inhibition of nitric oxide synthase.

The present study was designed to examine the role of nitric oxide (NO) in quinolinic acid (QUIN)-induced depletion of rat striatal nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase and enkephalinergic neurons. Intrastriatal injection of QUIN produced a dose-dependent decrease in NADPH diaphorase and enkephalin positive cells, with cell loss being evident following the injection of 6 and 18 nmol QUIN, respectively. To evaluate the role of NO in QUIN-induced toxicity, animals were pretreated with the non-specific nitric oxide synthase (NOS) inhibitor, Nomega-nitro-l-arginine (l-NAME) or the selective neuronal NOS inhibitor, 7-nitro indazole (7-NI). l-NAME (2x250 mg/kg, i.p. 8 h apart) maximally inhibited striatal NOS activity by 85%, while 7-NI (50 mg/kg, i.p.) maximally inhibited striatal NOS activity by 60%. Pretreatment with l-NAME or 7-NI potentiated the loss of NADPH diaphorase neurons resulting from intrastriatal injection of low doses of QUIN (18 nmol). Neither NOS inhibitor had any effect on the loss of striatal NADPH diaphorase neurons induced by a higher dose of QUIN (24 nmol). In contrast, 7-NI partially prevented the QUIN (18 and 24 nmol)-induced loss of enkephalinergic neurons, while l-NAME had no effect. These results indicate that NO formation may play a role in QUIN-induced loss of enkephalinergic neurons, but not in the loss of NADPH diaphorase neurons.

Animals↗