The influence of repeated administration of clozapine and haloperidol on the effects of the activation of 5-HT(1A), 5-HT(2) and 5-HT(4) receptors in rat frontal cortex.

The effects of a repeated treatment with antipsychotic drugs, clozapine and haloperidol, on the modulation of network activity ex vivo by 5-HT receptors were examined in rat frontal cortical slices using extracellular recording. Rats were treated for 21 days with clozapine (30 mg/kg p.o.), or haloperidol (1 mg/kg p.o.). Spontaneous bursting activity was induced in slices prepared 3 days after the last drug administration by perfusion with a medium devoid of Mg(2+) ions and with added picrotoxin (30 mM). The application of 2-3 microM 8-OH-DPAT, acting through 5-HT(1A) receptors, resulted in a reversible decrease of bursting frequency. In the presence of 1 microM DOI, the 5-HT(2) agonist, or 5 microM zacopride, the 5-HT(4) agonist, bursting frequency increased. Chronic clozapine treatment resulted in an attenuation of the effect of the activation of 5-HT(2) receptors, while the effects related to 5-HT(1A) and 5-HT(4) receptor activation were unchanged. Treatment with haloperiol did not influence the reactivity to the activation of any of the three 5-HT receptor subtypes. These data are consistent with earlier findings demonstrating a selective downregulation of 5-HT(2A) receptors by clozapine and indicate that chronic clozapine selectively attenuates the 5-HT-mediated excitation in neuronal circuitry of the frontal cortex while leaving the 5-HT-mediated inhibition intact.

Citation

A Zahorodna, B Bobula, M Grzegorzewska, K Tokarski, G Hess. The influence of repeated administration of clozapine and haloperidol on the effects of the activation of 5-HT(1A), 5-HT(2) and 5-HT(4) receptors in rat frontal cortex. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society. 2004 Jun;55(2):371-9

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PMID: 15213359

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