Detecting behaviorally relevant changes in extracellular dopamine with microdialysis

Church, William H.; Justice, Joseph B.; Neill, Darryl B.

doi:10.1016/0006-8993(87)91150-4

Cited by 136 publications

(39 citation statements)

References 5 publications

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“…However, a functional role for tonic DA and its regulation by glutamate may be predicted based on the following considerations: (1) The extracellular level of glutamate in the striatum (2-8IlM; Korf and Venema, 1985) is sufficient to tonically activate NMDA receptors (EDso = 51lM; Sands and Barish, 1989) as shown to occur in the hippocampus (Sah et al, 1989). (2) The extracellular level of DA in the striatum (10-50nM; Church et al, 1987;Sharp et al, 1986) should be sufficient to tonically activate D2 receptors (Kd = 40nM; Richfield et al, 1989) which, among other functions, will presynaptically inhibit spike-dependent DA release (Farnebo and Hamberger, 1971). (3) Each striatal neuron is estimated to receive 4,500-8,000 DA terminals, with half of these synapsing on the same dendritic spine as the corticostriatal afferents (Doucet et al, 1986), thus supplying each neuron with locally high concentrations of extracellular DA and glutamate.…”

Section: Systems Involved In the Induction Of Depolarization Blockmentioning

confidence: 99%

The depolarization block hypothesis of neuroleptic action: implications for the etiology and treatment of schizophrenia

Grace

1992

Advances in Neuroscience and Schizophrenia

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Summary. Antipsychotic drugs are known to block dopamine receptors soon after their administration, resulting in an increase in dopamine neuron firing and dopamine turnover. Nonetheless, antipsychotic drugs must be administered repeatedly to schizophrenics before therapeutic benefits are produced. Recordings from dopamine neurons in rats have revealed that chronic antipsychotic drug treatment results in the time-dependent inactivation of dopamine neuron firing via over-excitation, or depolarization block. Furthermore, the clinical profile of the response to antipsychotic drugs appears to correspond to the dopamine system affected: antipsychotic drugs that exert therapeutic actions in schizophrenics inactivate dopamine neuron firing in the limbic-related ventral tegmental area, whereas drugs that precipitate extrapyramidal side effects cause depolarization block of the motor-related substantia nigra dopamine cells.One factor that remains unresolved with regard to the actions of antipsychotic drugs is the relationship between dopamine turnover and depolarization block -i.e., why does a significant level of dopamine release or turnover remain after antipsychotic drug treatment if dopamine cells are no longer firing? We addressed this question using an acute model of neuroleptic-induced depolarization block. In this model, dopamine cells recorded in rats one month after partial dopamine lesions could be driven into depolarization block by the acute administration of moderate doses of haloperidol. However, similar doses of haloperidol, which were effective at increasing dopamine levels in the striatum of intact rats, failed to change dopamine levels in lesioned rats. This is consistent with a model in which neuroleptic drugs exert their therapeutic effects in schizophrenics by causing depolarization block in DA cells, thereby preventing further activation of dopamine neuron firing in response to external stimuli. Thus, attenuating the responsivity of the dopamine system to stimuli may be more relevant to the therapeutic actions of antipsychotic drugs than receptor blockade or decreases in absolute levels of dopamine, which could presumably be circumvented by homeostatic adaptations in this highly plastic system.

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Section: Systems Involved In the Induction Of Depolarization Blockmentioning

confidence: 99%

The depolarization block hypothesis of neuroleptic action: implications for the etiology and treatment of schizophrenia

Grace

1992

Advances in Neuroscience and Schizophrenia

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“…A concentric microdialysis probe, constructed as previously described (Church et al, 1987;Robinson and Whishaw, 1988;Abercrombie et al, 1989), was implanted in the dopamine-depleted striatum at the following coordinates relative to bregma and the skull with the skull flat(mm1: AP + 0.5, ML 3.0, DV -7.0. The microdialysis probe incorporated a dialysis membrane with a molecular-weight cut-off of 13,000 (SpectraiPor RC, Spectrum) and had an active dialyzing length of 3.5 mm and an external diameter of 250 pm.…”

Section: Pharmacological Manipulationsmentioning

confidence: 99%

D1 dopamine receptor-mediated induction ofzif268 andc-fos in the dopamine-depleted striatum: Differential regulation and independence from NMDA receptors

Keefe

Gerfen

1996

J. Comp. Neurol.

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Excitatory amino acid afferents from cerebral cortex and dopamine afferents from the substantia nigra synapse on common projection neurons in the striatum. Activation of D1 dopamine receptors increases immediate early gene expression in the striatum and conductance through the N-methyl-d-aspartate (NMDA) receptor. To examine the contribution of NMDA receptor activation to dopamine receptor-mediated responses, we determined the effects of intrastriatal administration of NMDA antagonists on immediate early gene expression in the striatum and rotational behavior induced by stimulation of the D1 receptor in rats with unilateral dopamine depletions. Systemic administration of SKF 38393 increased c-fos and zif268 mRNAs in the striatum and induced contralateral rotation. Intrastriatal infusion of the competitive NMDA receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)-propyl -1-phosphonic acid caused a dose-dependent attenuation of SKF 38393-induced rotation and partially decreased c-fos mRNA expression. However, D1-mediated increases in zif268 mRNA were not affected, except by the highest concentration of antagonist used (10 mM). Another competitive antagonist, 2-amino-5-phosphonovaleric acid, had similar effects. Like the competitive antagonists, intrastriatal infusion of the non-competitive NMDA antagonist MK-801 partially decreased c-fos, but not zif268, mRNA in the area around the microdialysis probe. However, unlike competitive antagonists, local infusion of 1 mM MK-801 potentiated D1-mediated increases in c-fos and zif268 mRNAs in lateral striatum. These data suggest that 1) some D1 dopamine receptor-mediated effects on striatal function are independent of ongoing NMDA receptor activation, whereas other effects are at least partially mediated by NMDA receptor activity in the striatum, and 2) competitive and non-competitive antagonists of the NMDA receptor differently affect D1-mediated immediate early gene expression in the striatum.

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“…Roberts & Koob, 1982). According to recent measurements of cocaine and dopamine levels in striatal dialysates following an intraperitoneal injection, a dose of lmgkg-' in a rat would be expected to give a brain cocaine level considerably less than 1 gM (Church et al, 1987;Nicolaysen et al, 1988). An injection of 10mgkg-1 gave a predicted brain cocaine level of about 3pm; this is reasonably consonant with the finding that the inhibitory effect of this dose of cocaine on rat ventral tegmental area neurones was small, and partly attributable to descending influences from the nucleus accumbens (Einhorn et al, 1988).…”

Section: Cocaine Inhibits Cellfiring By Blocking Dopamine Uptakementioning

confidence: 99%

Actions of cocaine on rat dopaminergic neurones in vitro

Lacey

Mercuri

North

1990

British J Pharmacology

121

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1 Intracellular recordings were made from neurones in vitro in the rat substantia nigra zona compacta and ventral tegmental area; the neurones had the characteristic properties of dopamine-containing cells, and fired action potentials spontaneously. 2 Cocaine (1-104uM) inhibited spontaneous firing, hyperpolarized the membrane and (in neurones voltage-clamped at -60 mV) caused an outward membrane current; the minimally effective concentration was 1 pm. These effects were blocked by sulpiride (30 nM-iIM).3 Dopamine (3-100yM) also inhibited firing, hyperpolarized and caused an outward current. These effects of dopamine were potentiated about five fold by cocaine (10 pM).4 It is concluded that cocaine (1-10pM) inhibits the firing and hyperpolarizes substantia nigra zona compacta neurones in vitro by blocking the uptake of dopamine which the cells continuously release.

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Detecting behaviorally relevant changes in extracellular dopamine with microdialysis

Cited by 136 publications

References 5 publications

The depolarization block hypothesis of neuroleptic action: implications for the etiology and treatment of schizophrenia

The depolarization block hypothesis of neuroleptic action: implications for the etiology and treatment of schizophrenia

D1 dopamine receptor-mediated induction ofzif268 andc-fos in the dopamine-depleted striatum: Differential regulation and independence from NMDA receptors

Actions of cocaine on rat dopaminergic neurones in vitro

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