Rats, pretreated with saline or GABA(A) antagonist bicuculline (BIC) at the doses of 2, 4, 6, 10 and 20 mg/kg, were injected with nicotine (NIC, 1 mg/kg) 30 min later. Tail-flick (TF) latencies were measured before (baseline) and three times at 10 min interval after pretreated compounds, continued every 10 min up to 1 hr after NIC injection. In all groups, median TF latencies did not change from the baseline for the first 30 min after the pretreatment. Following NIC alone (control) and in the group pretreated with 2 mg/kg BIC, 60% rats reached ceiling TF latencies (20 sec) lasting for 10 min. In groups with higher BIC doses (4 to 10 mg/kg), median TF latencies were in the range of 5-7 sec with 30% rats reaching the ceiling TF latencies. Following 20 mg/kg BIC, one out of five rats reached 20 sec; the median was in the range of 4-5 sec. Significantly lower responses were observed following 4 mg BIC and higher doses with no difference among the groups. In conclusion, our novel data show that BIC alone, injected systemically, does not possess any effect on the thermal nociceptive transmission as measured by the tail flick test. However, pretreatment with BIC partially prevents NIC-induced antinociception, in a non dose related manner. This suggests that GABA(A) receptors may, at least in part, contribute to the complex mechanisms involved in NIC-induced antinociception.