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

Stone, T.W.

doi:10.1111/j.1476-5381.1976.tb06964.x

Cited by 42 publications

(6 citation statements)

References 48 publications

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“…2c and e), and the well‐documented dampening effects on PFC neuronal activity (Mora et al. 1976; Stone 1976; Homayoun and Moghaddam 2006; Gulley and Stanis 2010) and synaptic transmission (Mair and Kauer 2007) by amphetamine at high doses/concentrations may also contribute to hyperdopaminergic impairments of LTP. In addition, negative priming (Sun et al.…”

Section: Discussionmentioning

confidence: 98%

Amphetamine modulation of long‐term potentiation in the prefrontal cortex: dose dependency, monoaminergic contributions, and paradoxical rescue in hyperdopaminergic mutant

Spealman

et al. 2010

Journal of Neurochemistry

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Amphetamine can improve cognition in healthy subjects and patients with schizophrenia, attention-deficit hyperactivity disorder (ADHD), and other neuropsychiatric diseases; higher doses, however, can impair cognitive function, especially those mediated by the prefrontal cortex (PFC). We investigated how amphetamine affects PFC long-term potentiation (LTP), a cellular correlate of learning and memory, in normal and hyperdopaminergic mice lacking the dopamine transporter (DAT-KO). Acute amphetamine treatment in wild-type mice produced a biphasic dose-response modulation of LTP, with a low dose enhancing LTP and a high dose impairing it. Amphetamine-induced LTP enhancement was prevented by pharmacological blockade of D1- (but not D2-) class dopamine receptors, by blockade of β-adrenergic receptors, or by inhibition of cAMP-PKA signaling. In contrast, amphetamine-induced LTP impairment was prevented by inhibition of postsynaptic protein phosphatase-1 (PP1), a downstream target of PKA signaling, or by blockade of either D1- or D2-class dopamine, but not noradrenergic, receptors. Thus, amphetamine biphasically modulates LTP via cAMP-PKA signaling orchestrated mainly through dopamine receptors. Unexpectedly, amphetamine restored the loss of LTP in DAT-KO mice primarily by activation of the noradrenergic system. Our results mirror the biphasic effectiveness of amphetamine in humans and provide new mechanistic insights into its effects on cognition under normal and hyperdopaminergic conditions.

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Section: Discussionmentioning

confidence: 98%

Amphetamine modulation of long‐term potentiation in the prefrontal cortex: dose dependency, monoaminergic contributions, and paradoxical rescue in hyperdopaminergic mutant

Spealman

et al. 2010

Journal of Neurochemistry

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“…Amphetamine iontophoresis inhibited activity [26, 27]. Systemic injection in anesthetized [28, 29] or awake animals [30, 31], decreased FR at lower doses and increased FR at higher doses.…”

Section: Discussionmentioning

confidence: 99%

Amphetamine's dose-dependent effects on dorsolateral striatum sensorimotor neuron firing

Pawlak

Cho

et al. 2013

Behavioural Brain Research

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Amphetamine elicits motoric changes by increasing the activity of central neurotransmitters such as dopamine and serotonin, but how these neurochemical signals are transduced into motor commands is unclear. The dorsolateral striatum (DLS), a component of the cortico-subcortical reentrant motor loop, contains abundant neurotransmitter transporters that amphetamine could affect. It has been hypothesized that DLS medium spiny neurons contribute to amphetamine’s motor effects. To study striatal activity contributing to amphetamine-induced movements, activity of DLS neurons related to vertical head movement was recorded while tracking head movements before and after acute amphetamine injection. Relative to saline, all amphetamine doses induced head movements above pre-injection levels, revealing an inverted U-shaped dose-response function. Lower doses (1mg/kg and 2 mg/kg, intraperitoneal) induced a greater number of long (distance and duration) movements than the high dose (4 mg/kg), which induced stereotypy. Firing rates (FR) of individual head movement neurons were compared before and after injection during similar head movements, defined by direction, distance, duration, and apex. Changes in FR induced by amphetamine were co-determined by dose and pre-injection FR of the neuron. Specifically, all doses increased the FRs of slower firing neurons but decreased the FRs of faster firing neurons. The magnitudes of elevation or reduction were greater at lower doses, but less pronounced at the high dose, forming an inverted U function. Modulation of DLS firing may interfere with sensorimotor processing. Furthermore, pervasive elevation of slow firing neurons’ FRs may feed-forward and increase excitability in thalamocortical premotor areas, contributing to the increased movement initiation rate.

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

Cited by 42 publications

References 48 publications

Amphetamine modulation of long‐term potentiation in the prefrontal cortex: dose dependency, monoaminergic contributions, and paradoxical rescue in hyperdopaminergic mutant

Amphetamine modulation of long‐term potentiation in the prefrontal cortex: dose dependency, monoaminergic contributions, and paradoxical rescue in hyperdopaminergic mutant

Amphetamine's dose-dependent effects on dorsolateral striatum sensorimotor neuron firing

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

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