¹Paulista University, Program in Environmental and Experimental Pathology, São Paulo, Brazil

Background: Panic disorder has a high prevalence; however, there is no fully integrative experimental model for its study. Existing models are mainly based on the evaluation of escape responses induced by aversive stimuli, and the underlying mechanisms are still not fully understood. One hypothesis involves the activation of serotonergic pathway in specific brain areas. Current treatments for panic disorder include psychological and pharmacological interventions, such as antidepressants–especially selective serotonin reuptake inhibitors (e.g., fluoxetine)–and benzodiazepines, such as alprazolam, among others. Due to the relatively low efficiency of these treatments, other medications have been investigated. Tramadol, an analgesic drug, has been shown to induce panicolytic-like effects in rats. Although it primarily acts on the opioid system, tramadol also modulates the monoaminergic system by inhibiting the reuptake of norepinephrine and serotonin.

Aims & Objectives: The aim of this study was to investigate the mechanisms underlying the panicolytic-like effects of tramadol.

Method: Adult male Wistar rats were used. Body weight was assessed. Rats were treated with tramadol (tramadol hydrochloride, Hipolabor, Belo Horizonte, Brazil; i.p., 32 mg/kg) or vehicle to induce panicolytic-like behavior. Thirty minutes after treatment, both control and tramadol-treated rats were subjected to an elevated T-maze model to induce and evaluate panic-like behaviors. Hypothalamic serotonin and norepinephrine levels were subsequently measured using ELISA.

Results: No statistically significant differences in body weight were observed between the groups. Inhibitory avoidance was not affected by tramadol treatment; however, escape latency was significantly increased compared to the control group. These findings indicate that tramadol induced panicolytic-like effect in rats. Hypothalamic serotonin levels were not altered by tramadol treatment, whereas hypothalamic norepinephrine levels were significantly increased compared to controls.

Discussion & Conclusions: In conclusion, tramadol induced panicolytic-like effects in rats through the modulation of hypothalamic norepinephrine.