Role of serotonin receptors in panic-like behavior induced by nitric oxide in the rat dorsolateral periaqueductal gray: effects of chronic clomipramine treatment.
Local administration of serotonin (5-HT) receptor agonists inhibits panic-like reactions induced by electrical stimulation of the rat dorsolateral periaqueductal grey (dlPAG). This anti-aversive effect is enhanced by chronic treatment with anti-panic drugs such as clomipramine. Since nitric oxide (NO) may mediate panic-like behavior in the dlPAG, we tested the hypothesis that chronic clomipramine treatment would also potentiate the effects of locally injected 5-HT-receptor agonists on panic-like reactions induced by intra-dlPAG injection of an NO-donor (SIN). After 21 days of daily i.p. injections of saline or clomipramine (10 mg/kg) male Wistar rats received local injections of saline, the 5-HT(1A)-receptor agonist 8-OH-DPAT (8 nmol) or the 5-HT2A/2C-receptor agonist DOI (16 nmol) followed by saline or SIN (150 nmol). NO-induced panic-like reactions were inhibited by DOI, but not by 8-OH-DPAT. Chronic clomipramine did not modify these effects but tended to produce anti-aversive effect by itself. In chronically clomipramine treated animals 8-OH-DPAT potentiated NO-induced panic-like reactions. The results indicate that the panic-like effects of NO in the dlPAG may be attenuated by 5-HT2A/2C-, but not by 5-HT1A-receptors. The anti-aversive effect of DOI is not modified by chronic clomipramine treatment.
Moreira
Fabrício Araújo
FA
Department of Pharmacology, FMRP, Campus USP, 14049-900, Ribeirão Preto, SP, Brazil.
Guimarães
Francisco Silveira
FS
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002997:Clomipramine / Q000494:pharmacology*; D006652:Histological Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010200:Panic / Q000187:drug effects* / Q000502:physiology; D010487:Periaqueductal Gray / Q000033:anatomy & histology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000662:Amphetamines; D017366:Serotonin Receptor Agonists; D009569:Nitric Oxide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002997:Clomipramine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine