Antidepressant-like effect of lead in adult mice

Abstract

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.

Motor behavior and brain enzymatic changes after acute lead intoxication on different strains of mice

“…In the present work, the mice were 40-55 days old and, presumably they were in a life period with less vulnerability to toxicants such as lead relative to younger animals (Booze and Mactutus, 1990). As with our results, other authors also have found no modification of locomotor behavior in adult Swiss mice (Mantovani et al, 1999). Moreover, older Swiss mice (115 days old) injected with 100 mg/kg lead acetate i.p.…”

“…Moreover, older Swiss mice (115 days old) injected with 100 mg/kg lead acetate i.p. demonstrated no effects on body weight or spontaneous locomotion compared to saline treated mice of the same age (Mantovani et al, 1999). Although spontaneous locomotion was not affected seven days after lead administration in any of the strains tested, there was evidence of strain differences in the effects of lead on body weight.…”

Effects of developmental stress and lead (Pb) on corticosterone after chronic and acute stress, brain monoamines, and blood Pb levels in rats

“…Gavage was used to avoid maternal exposure. Pb is known to affect adult behavior (Cory‐Slechta and Weiss, 1989; Mantovani et al, 1999; Massaro et al, 1986; Yun et al, 2000) which could affect dam behavior, including maternal care. A preliminary experiment on the effect of gavage showed that giving water on P4 did not significantly increase CORT levels 30 min later compared to non‐gavaged rats.…”

The role of mood stabilisers in the treatment of the depressive facet of bipolar disorders

“…For example, functional antagonists of the N-methyl-D-aspartate (NMDA) complex (e.g. competitive and non-competitive receptor antagonists, and glycine partial agonists) exhibit an antidepressant-like effect in animal models of depression (Trullas and Skolnick, 1990;Mantovani et al, 1999;Petrie et al, 2000;Paul and Skolnick, 2003). Moreover, chronic, but not acute, treatment with several clinically effective antidepressants drugs (22 of 23 drugs tested) reduced the potency of glycine in inhibiting the [3H]-5, 7-dichlorkynurenic acid (5, 7-DCKA) binding to strychnine-insensitive glycine site (Paul et al, 1994).…”