Evidence for dual effects of nitric oxide in the forced swimming test and in the tail suspension test in mice.

L-Arginine (L-Arg), a substrate for nitric oxide synthase (NOS) at a dose of 250-500 mg/kg, i.p., significantly reduced the duration of immobility both in the forced swimming test (FST) and in the tail suspension test (TST), two models of depression in mice, without changing locomotion in an open field. Paradoxically, a similar effect was observed with the administration of N(G)-nitro-L-arginine (L-NNA) (0.3-10 mg/kg, i.p.), an inhibitor of NOS. However, higher doses of L-Arg (750-1000 mg/kg) and L-NNA (30 mg/kg) did not produce any anti-immobility effect in FST and TST. The inactive isomers D-Arg (100-1000 mg/kg, i.p.) and D-NNA (0.3-30 mg/kg, i.p.) did not affect immobility duration in either the FST and TST. Preadministration of L-NNA (30 mg/kg, i.p.), but not of D-NNA completely blocked the anti-immobility effect of L-Arg (500 mg/kg, i.p.) in the FST. Similarly, L-Arg (750 mg/kg, i.p.), but not D-Arg blocked the anti-immobility effect of L-NNA (3 mg/kg, i.p.) in the FST. The results indicate that either the synthesis of NO or the inhibition of its synthesis may produce antidepressant-like effects when assessed in the FST and TST. The physiological meaning of this finding is still obscure, but it could indicate that NO has a dual role in the modulation of depression.

Antidepressant-like effect of lead in adult mice.

It has been reported that lead can cause behavioral impairment by inhibiting the N-methyl-D-aspartate (NMDA) receptor complex. MK-801, a noncompetitive NMDA receptor antagonist, exhibits an antidepressant-like action in the forced swimming test. The purpose of the present study was to determine whether subacute lead exposure in adult male Swiss mice weighing 30-35 g causes an antidepressant-like action in a forced swimming test. Mice were injected intraperitoneally (ip) with 10 mg/kg lead acetate or saline daily for 7 consecutive 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 saline and were tested in forced swimming and in open-field tests. Immobility time was similarly reduced in the saline-MK-801, Pb-saline and Pb-MK-801 groups 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). These data indicate that lead may exert its effect on the forced swimming test by directly or indirectly inhibiting the NMDA receptor complex. Lead treatment 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 after lead exhibited a deficit in habituation (22% reduction in rearing responses between session 3 and 1; N = 14) as compared to control (41% reduction in rearing responses; N = 15), further suggesting that lead may have affected the NMDA receptor activity. Forced-swim immobility in a basin in two daily 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 compared 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 indicating a specific antidepressant-like action of lead.

Antidepressant-like effect of lead in adult mice

It has been reported that lead can cause behavioral impairment by inhibiting the N-methyl-D-aspartate (NMDA) receptor complex. MK-801, a noncompetitive NMDA receptor antagonist, exhibits an antidepressant-like action in the forced swimming test. The purpose of the present study was to determine whether subacute lead exposure in adult male Swiss mice weighing 30-35 g causes an antidepressant-like action in a forced swimming test. Mice were injected intraperitoneally (ip) with 10 mg/kg lead acetate or saline daily for 7 consecutive 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 saline and were tested in forced swimming and in open-field tests. Immobility time was similarly reduced in the saline-MK-801, Pb-saline and Pb-MK-801 groups compared to the saline-saline group (mean + or - SEM; 197.3 + or - 18.5, 193.5 + or - 15.8, 191.3 + or - 12.3 and 264.0 + or - 14.4 s, respectively; N = 9). These data indicate that lead may exert its effect on the forced swimming test by directly or indirectly inhibiting the NMDA receptor complex. Lead treatment 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 after lead exhibited a deficit in habituation (22 per cent reduction in rearing responses between session 3 and 1; N = 14) as compared to control (41 per cent reduction in rearing responses; N = 15), further suggesting that lead may have affected the NMDA receptor activity. Forced-swim immobility in a basin in two daily consecutive sessions was also significantly decreased by lead exposure (mean + or - SEM; day 1 = 10.6 + or - 3.2, day 2 = 19.6 + or - 3.6; N = 16) as compared to control (day 1 = 18.4 + or - 3.8, day 2 = 34.0 + or - 3.7; N = 17), whereas the number of crossings was not affected by lead treatment, further indicating a specific antidepressant-like action of lead.