Effect of antipsychotic drugs and selective dopaminergic antagonists on dopamine-induced facilitatory activity in prelimbic cortical pyramidal neurons. An in vitro study
Section snippets
Animals
Male CD-COBS rats (Charles River, Italy) weighing 150–250 g, were housed under a 12 h off light–dark schedule (7.00 a.m.–7.00 p.m.) with constant room temperature (20±1°C) and free access to food and water. The animal care and handling was conducted in compliance with the European Communities Council Directive of 24 November 1986 (86/609/ECC).
Preparation of prefrontocortical slices
The rats were killed and their brains were rapidly removed and placed in ice-cold artificial cerebrospinal fluid (ACSF) solution (in mM): NaCl 124, KCl 5, MgSO
Passive membrane properties of medial prefrontal cortex pyramidal neurons
In this study, 128 pyramidal neurons located within the mPFC were investigated. The cells studied were selected on the basis of having a stable resting membrane potential of at least −60 mV, a spike amplitude >70 mV, and a spike overshoot of >10 mV. All the neurons were silent at rest and could be recorded for periods ranging from 15 min to 5 h.
The electrophysiological characterization of six pyramidal neurons was performed in the middle level of the PrL. The passive membrane properties of these
Discussion
The main finding of this study was that DA had a facilitatory effect on electrically stimulated mPFC pyramidal neurons localized specifically in the middle layer of the PrL, which is a subregion of mPFC, and this effect was antagonized by antipsychotic drugs and by the selective D4 antagonist L-745,870.13 In two other subregions of the mPFC, i.e. the CG1 and IL, DA was inactive.
The passive membrane properties of these neurons (i.e. resting membrane potential, input membrane resistance, shape of
Conclusion
It has been suggested that D4 receptors may be implicated in schizophrenia based upon their prevalence in the prefrontal cortical system, and because most antipsychotic drugs have high affinity for this receptor.2., 25., 32. On the other hand, the selective D4 antagonist, L-745,870,13 failed in the treatment of schizophrenia.7 The present study clearly shows that L-745,870 has a pharmacological effect similar to antipsychotics on pyramidal neurons localized in the middle layer of PrL. However,
References (36)
- et al.
Cellular distribution of the rat D4 dopamine receptor protein in the CNS using anti-receptor antisera
Brain Res.
(1997) - et al.
Responses of intracellularly recorded cortical neurons to the iontophoretic application of dopamine
Brain Res.
(1982) - et al.
Schizophrenia and L-745,870, a novel dopamine D4 receptor antagonist
Trends pharmac. Sci.
(1997) - et al.
Dopamine and norepinephrine innervated cells in the rat prefrontal cortex: pharmacological differentiation using microiontophoretic techniques
Life Sci.
(1976) - et al.
Intrinsic firing patterns of diverse neocortical neurons
Trends Neurosci.
(1990) - et al.
Dopamine and schizophrenia B a cortically corrective perspective
Semin. Neurosci.
(1992) - et al.
Differential effects of ascending neurons containing dopamine and noradrenaline in the control of spontaneous activity and of evoked responses in the rat prefrontal cortex
Neuroscience
(1988) - et al.
Electrical stimulation of mesencephalic cell groups (A9–A10) produces monosynaptic excitatory potentials in rat frontal cortex
Brain Res.
(1985) - et al.
Changes in extracellular brain ascorbate in rat striatum in response to administration of non-volatile anaesthetic agents
Br. J. Anaesth.
(1997) - et al.
Excitatory of rat prefrontal cortical neurons by dopamine: an in vitro electrophysiological study
Brain Res.
(1987)
Inhibitory effects of ventral tegmental area stimulation on the activity of prefrontal cortical neurons: evidence for the involvement of both dopaminergic and GABAergic components
Neuroscience
Dopamine receptor pharmacology
Trends pharmac. Sci.
Microiontophoretic application of some monoamines and their antagonists to cortical neurones of the rat
Neuropharmacology
Dopaminergic modulation of cholinergic responses in rat medial prefrontal cortex: an electrophysiological study
Brain Res.
Differential electroresponsiveness of stellate and pyramidal-like cells of medial entorhinal cortex layer II
J. Neurophysiol.
Quantitative autoradiographic localization of the D1 and D2 subtypes of dopamine receptors in rat brain
J. Neurosci.
Excitatory neuronal responses to dopamine in the cerebral cortex: involvement of D2 but not D1 dopamine receptors
Br. J. Pharmac.
Activation of the 5-HT1C receptor expressed in Xenopus oocytes by the benzazepine SCH 23390 and SKF 38393
Br. J. Pharmac.
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2014, Biological PsychiatryCitation Excerpt :Electrophysiological recordings within the prefrontal cortex (PFC) provide some support for this suggestion. D4 receptor activation within the PFC can control the modulatory effect of basolateral amygdala (BLA) input on the spontaneous activity of PFC pyramidal neurons, suppressing BLA-evoked inhibition (63) and appears to enhance the excitatory effect of DA on network activity by reducing feed-forward inhibition (64,65). A recent theory ventured by Lauzon and Laviolette (32) posits that activation of D4 receptors in the PFC can therefore amplify the emotional salience of environmental stimuli by boosting the facilitatory effects of inputs from both the ventral tegmental area and BLA on pyramidal neuron firing (32), inputs known to convey information regarding the affective properties of cues.