Antidepressant-like effect of lead in adult mice

It has been reported that lead can cause behavioral impairment by inhibitin g the N-methyl-D-aspartate (NMDA) receptor complex. MK-801, a noncompetitiv e NMDA receptor antagonist, exhibits an antidepressant-like action in the f orced swimming test. The purpose of the present study was to determine whet her subacute lead exposure in adult male Swiss mice weighing 30-35 g causes an antidepressant-like action in a forced swimming test. Mice were injecte d intraperitoneally (ip) with 10 mg/kg lead acetate or saline daily for 7 c onsecutive days. Twenty-four hours after the last treatment, the saline and lead-treated mice received an injection of MK-801 (0.01 mg/kg, ip) or sali ne and were tested in forced swimming and in open-field tests. Immobility t ime was similarly reduced in the saline-MK-801, Pb-saline and Pb-MK-801 gro ups compared to the saline-saline group (mean +/- SEM; 197.3 +/- 18.5, 193. 5 +/- 15.8, 191.3 +/- 12.3 and 264.0 +/- 14.4 s, respectively; N = 9). Thes e data indicate that lead may exert its effect on the forced swimming test by directly or indirectly inhibiting the NMDA receptor complex. Lead treatm ent caused no deficit in memory of habituation and did not affect locomotor activity in an open-field (N = 14). However, mice that received MK-801 aft er lead exhibited a deficit in habituation (22% reduction in rearing respon ses between session 3 and 1; N = 14) as compared to control (41% reduction in rearing responses; N = 15), further suggesting that lead may have affect ed the NMDA receptor activity. Forced-swim immobility in a basin in two dai ly consecutive sessions was also significantly decreased by lead exposure ( mean +/- SEM; day 1 = 10.6 +/- 3.2, day 2 = 19.6 +/- 3.6; N = 16) as compar ed to control (day 1 = 18.4 +/- 3.8, day 2 = 34.0 +/- 3.7; N = 17), whereas the number of crossings was not affected by lead treatment, further indica ting a specific antidepressant-like action of lead.