Effects of acute and chronic fluoxetine and diazepam on freezing behavior induced by electrical stimulation of dorsolateral and lateral columns of the periaqueductal gray matter

Abstract

The defensive responses induced by electrical stimulation of the dorsal periaqueductal gray matter (dPAG) of the rat have been proposed as a model of panic attacks in humans. In the present study we investigated the acute and chronic effects of fluoxetine and diazepam on freezing and escape reactions elicited by electrical stimulation of the dorsolateral (dlPAG) and lateral (lPAG) columns of the periaqueductal gray matter (PAG). The frequencies of crossing, rearing, bouts of micturition and fecal boli were also recorded. Electrodes were unilaterally implanted in the brainstem aimed at the PAG. Drug treatments were given daily for 2 weeks with fluoxetine (5, 10 and 20 mg/kg ip), a selective inhibitor of serotonin reuptake, diazepam (1, 2 and 4 mg/kg ip), or saline. Drug effects were assessed acutely (15 min after the first injection) and chronically (15 min after the 14th injection). Chronic, but not acute, administration of fluoxetine caused a significant increase in the threshold of freezing without affecting the escape response elicited by dlPAG/lPAG stimulation. This characteristic pattern of effects could not be attributed to motor deficit, since this drug did not change the number of crossings and rearings. In contrast, no significant threshold changes were observed following acute and chronic treatment with diazepam. These data give further evidence for (a) an antiaversive effect of chronic treatment with fluoxetine, which caused a selective reduction in freezing behavior and neurovegetative responses associated with fearlike reaction elicited by dlPAG/lPAG electrical stimulation; (b) the involvement of the dlPAG and lPAG in the generation and organization of defensive responses and that freezing may probably be associated with panic attacks; and (c) the lack of effect of diazepam in this model is in line with its inefficacy as a panicolytic drug. The study of the unconditioned freezing behavior evoked by dlPAG/lPAG stimulation may constitute a new and interesting model for the study of panic disorder.