Elsevier

Neuroscience

Volume 93, Issue 1, June 1999, Pages 107-115
Neuroscience

Effect of antipsychotic drugs and selective dopaminergic antagonists on dopamine-induced facilitatory activity in prelimbic cortical pyramidal neurons. An in vitro study

https://doi.org/10.1016/S0306-4522(99)00123-2Get rights and content

Abstract

Intracellular recordings were obtained from 119 pyramidal neurons localized in prelimbic cortex, five in the dorsal cingulate cortex, one in the infralimbic cortex, one in the border of prelimbic and cingulate cortex and two in the border of prelimbic and infralimbic cortex. The passive membrane properties of these pyramidal neurons (i.e. resting membrane potential, input membrane resistance, shape of the tetrodotoxin-sensitive action potentials, spike frequency adaptation with a prominent postspike afterhyperpolarization, tetrodotoxin-sensitive inward rectification in the depolarizing direction and the absence of bursting) suggested that they resembled regular spiking or intrinsically bursting pyramidal neurons. Bath application of dopamine (EC50 of 1.8 μM) produced a reversible facilitatory effect on all 119 pyramidal neurons localized in the middle layer of the prelimbic cortex. No consistent change in membrane potential was detected during the application of dopamine. No effect of dopamine was noted on the nine pyramidal neurons that were not localized in the prelimbic cortex. The facilitatory effect of dopamine in prelimbic cortex was concentration dependently antagonized by haloperidol, risperidone, quetiapine, clozapine and by the selective D4 dopaminergic receptor antagonist L-745,870, but not by the selective D2/D3 dopaminergic receptor antagonist (−)-sulpiride. (+)-SCH 23390, which is a selective D1/D5 dopamine receptor antagonist, produced, similarly to dopamine, a facilitatory effect per se, and an additive effect when co-administered with dopamine.

These results provide evidence that dopamine has a facilitatory effect specifically on pyramidal neurons localized in the middle layer of prelimbic cortex. Antipsychotic drugs and L-745,870 block this effect of dopamine.

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,

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