Microiontophoretic studies of the effects of false transmitter candidates and amphetamine on cerebellar Purkinje cells

Kostopoulos, George; Yarbrough, George G.

doi:10.1111/j.2042-7158.1975.tb09469.x

Cited by 20 publications

(6 citation statements)

References 17 publications

(5 reference statements)

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“…However, several other groups have found no difference between neuronal responses to amphetamine in control rats and rats pretreated with reserpine or 6-hydroxydopamine (Hoffer, Siggins & Bloom, 1971;Feltz & de Champlain, 1972b;Kostopoulos & Yarbrough, 1974). 6-Hydroxydopamine produces a profound loss of catecholamines and aminergic terminals from treated areas of the brain, so that these observations support the possibility that amphetamine can act directly on postsynaptic receptors.…”

Section: Studies Ofamine-depleted Ratssupporting

confidence: 56%

Responses of Neurones in the Cerebral Cortex and Caudate Nucleus to Amantadine, Amphetamine and Dopamine

Stone

1976

British J Pharmacology

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I Dopamine, amantadine and amphetamine have been applied directly by microiontophoresis to single neurones in the caudate nucleus ana cerebral cortex of rats anaesthetized with urethane. 2 The predominant response to all three agents was a depression of neuronal firing rate. The responses to dopamine and amantadine could be antagonized by the dopamine receptor blocking agent, chlorpromazine. 3 Amantadine did not cause any potentiation of dopamine responses, suggesting that inhibition of amine uptake was not responsible for its effects. 4 The responses of pyramidal tract cells in the cerebral cortex to dopamine, amphetamine and amantadine were compared in control groups of rats and rats pretreated with reserpine (10 mg/kg i.p.) or a-methyl-p-tyrosine methyl ester (200 mg/kg i.p.). The reduction of cortical catecholamine concentrations was confirmed by a direct fluorimetric assay method. 5Responses to dopamine were unaltered in the amine-depleted animals compared with controls. Responses to amantadine and amphetamine were reduced but not abolished. -6 It is concluded that amantadine acts partly by releasing catecholamines from neuronal stores. The residual responses to amantadine and amphetamine may be the result of a direct postsynaptic receptor stimulation.

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Section: Studies Ofamine-depleted Ratssupporting

confidence: 56%

Responses of Neurones in the Cerebral Cortex and Caudate Nucleus to Amantadine, Amphetamine and Dopamine

Stone

1976

British J Pharmacology

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“…Amphetamine is classically an indirect agonist (Weiner, 1972); generally its electrophysiological effects in caudate after parenteral administration disappear with lesion of catecholamine pathways by 6-OHDA (Groves et al, 1975). Despite this clear role as an indirect agonist, locally administered amphetamine has been shown in five studies to have direct effects after amine depletion or lesion of dopaminergic (Feltz and de Champlain, 1972;Stone, 1976) or noradrenergic (Hoffer et al, 1971(Hoffer et al, , 1975Kostopoulos and Yarbrough, 1974) circuits. PCP, on the other hand, has no direct dopaminergic (Johnson et al, 1984) or noradrenergic (Marwaha et al, 1980) effects, even when applied locally to 6-OHDA-lesioned animals.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the failure of parenterally administered haloperidol to antagonize dopamine released from micropipettes in the caudate

Johnson¹,

Hoffer²,

Freedman³

1986

J. Neurosci.

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An anomaly in the experimental data underlying the theory that neuroleptics act by blockade of dopaminergic neurotransmission is the repeatedly demonstrated failure in several laboratories of parenterally administered neuroleptics to antagonize electrophysiologic actions of locally applied dopamine (DA) in striaturn. This failure is enigmatic since many investigators have successfully demonstrated antagonism when both dopamine and neuroleptic are applied directly to striatal neurons by microiontophoresis. We used multibarrel micropipettes to pressure-eject DA agonists onto rat caudate neurons while observing the ability of parenterally administered haloperidol to block the inhibitory actions of dopaminergic agonists on neuronal activity. Experiments performed at times of maximal behavioral effect of haloperidol did not demonstrate agonist-antagonist interaction. This result has been obtained by four other teams of investigators. A variety of pharmacologic manipulations were employed to help solve this enigma. Acute treatment with reserpine and a-methyl-paratyrosine, performed to minimize any possible interference by endogenous DA, did not permit blockade of dopamine by haloperidol. To see if this failure of antagonism could be generalized to other DA agonists, apomorphine, amphetamine, and phencyclidine (PCP) were also investigated. Although the direct dopaminergic agonist apomorphine was not antagonized by haloperidol, the indirect DA agonist PCP was successfully antagonized. Amphetamine, which has both direct and indirect actions when applied locally, was not antagonized. Antagonism of direct agonists was demonstrated in rats with unilateral 6-hydroxydopamine-induced lesions of the nigrostriatal pathway. In these preparations, parenterally administered haloperidol reversed the receptor-mediated supersensitivity to the inhibitory effects of locally applied DA and apomorphine. These data suggest that in caudate there exist postsynaptic receptors that are more sensitive to haloperidol than those receptors usually activated by DA released into the neuronal milieu from micropipettes. We suggest that PCP's indirect action on endogenous DA in presynaptic terminals results in specific interaction with these receptors. We further suggest that the postsynaptic receptors most sensitive to blockade by haloperidol may also be those receptors that increase in number following denervation. Failure to demonstrate antagonism of direct DA agonists in the absence of supersensitivity suggests that locally applied DA does not normally contact postsynaptic dopami-

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“…a 1 -Agonists, but not a 2 -or b-agonists, increase cytoplasmic calcium signaling in cerebellar Purkinje neurons (Kirischuk et al 1996). It has been reported that MA may directly and indirectly interact with a-adrenergic receptors (Smith 1963;Kostopoulos and Yarbrough 1975;Wang et al 1995). In this study, we found that following blockade of a-receptors with prazocin, MA potentiates GABA-induced inhibition, suggesting MA may produce a negative modulatory e¤ect on GABA action through a-receptors.…”

Section: Discussionmentioning

confidence: 63%

“…It has been demonstrated, using microdialysis, that systemic application of amphetamine (2 mg / kg, IP) increases NE release from a basal level of 810 pg / 20 µl to 400 450 pg / 20 µl in the cerebellum (Krobert et al 1994). On the other hand, amphetamine also directly acts on post-synaptic noradrenergic receptors (Smith 1963;Kostopoulos and Yarbrough 1975). Therefore, methamphetamine (MA) may modify GABA-induced e¤ects via noradrenergic mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Methamphetamine modulates GABA-induced electrophysiological depression by alternating noradrenergic actions in cerebellar Purkinje neurons

Jeng

Wang

1998

Psychopharmacology

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Previous studies have indicated that gamma-aminobutyric acid (GABA)-induced electrophysiological responses can be enhanced by noradrenaline (NE) acting via beta-adrenergic receptors. Methamphetamine (MA) has been reported to be a noradrenergic releasing agent. In the present study, we examined the interaction of MA and GABA in cerebellar Purkinje neurons of urethane-anesthetized rats. We found that local application of MA did not potentiate GABA-induced electrophysiological depressions in Purkinje neurons. Since MA may act indirectly or directly on alpha or beta noradrenergic receptors, we further examined the interactions of MA with selective noradrenergic antagonists. We found that after blocking alpha-adrenergic receptors with prazocin, MA significantly facilitated GABA responses. On the other hand, co-administration of timolol with MA did not attenuate GABA-induced neuronal depressions. To examine further the interactions between alpha and beta receptors in modulating GABA response, we found that stimulation of alpha-adrenergic receptors in the absence of beta receptor activation, such as by application of the alpha-agonist phenylephrine alone, did not decrease GABA-induced inhibition. However, stimulation of alpha-adrenergic receptors in the presence of beta-receptor activation, such as by co-application of phenylephrine and the beta-agonist isoproterenol (ISO), attenuated ISO-facilitated GABA inhibition. Taken together, these data suggest that MA may activate two noradrenergic modulatory mechanisms: beta-adrenergic receptor-induced GABA potentiation and alpha-adrenergic inhibition, which attenuates beta-mediated modulation. In conclusion, our data suggest that MA may regulate GABA-induced electrophysiological response by altering both the alpha- and beta-noradrenergic inputs in cerebellar Purkinje neurons.

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Microiontophoretic studies of the effects of false transmitter candidates and amphetamine on cerebellar Purkinje cells

Cited by 20 publications

References 17 publications

Responses of Neurones in the Cerebral Cortex and Caudate Nucleus to Amantadine, Amphetamine and Dopamine

Responses of Neurones in the Cerebral Cortex and Caudate Nucleus to Amantadine, Amphetamine and Dopamine

Investigation of the failure of parenterally administered haloperidol to antagonize dopamine released from micropipettes in the caudate

Methamphetamine modulates GABA-induced electrophysiological depression by alternating noradrenergic actions in cerebellar Purkinje neurons

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