The 5-HT1A receptor agonist flesinoxan increases aversion in a model of panic-like anxiety in rats

Acute systemic administration of the selective serotonin (5-HT)(1A) recepto r full agonist flesinoxan enhanced the sensitivity of rats to the panic-lik e aversion elicited by local stimulation of the dorsolateral periaqueductal grey (dPAG). This experimental paradigm in rats has previously been valida ted as a simulation of acute anxiety with particular relevance to panic dis order. The dose-dependent decrease in threshold for acute fear responses re corded in rats following intraperitoneal administration of flesinoxan (1-10 mg/kg) was similar to that induced by the panic precipitating agent yohimbi ne and opposite to the threshold increase induced by the antipanic drug alp razolam. The proaversive effect of flesinoxan observed in rats is consisten t with the reported aggravation of the condition of panic patients followin g oral flesinoxan treatment. Thus, the model adequately detects drug-induce d panicogenic-like properties. Data suggest that selective activation of 5- HT1A receptors (pre- and/or post-synaptic in brain and/or periphery) follow ing systemic administration of 5-HT1A receptor full agonists exacerbates av ersion in animals or patients with panic anxiety; activation of these recep tor subtypes may probably mediate the panicogenic action reported under cer tain circumstances with non-selective 5-HT mimetics.