AIMS: The precise neurochemical perturbations through which perinatal (gestation/lactation) lead exposure modifies the reinforcement efficacy of various psychoactive drugs (e.g., cocaine, opiates) are unknown. The present study considers the role of altered serotonin and dopamine functionality in perinatal lead-psychostimulant interactions. MAIN METHODS: Female rats were administered a 16-mg lead or a control solution (p.o.) for 30days prior to breeding with non-exposed males. Lead exposure was discontinued at weaning (postnatal day [PND] 21). Starting at PND 120, male rats born to control or lead-exposed dams were injected with either PAL-287 or PAL-353, at doses of 0, 2, 4, 8, or 16umol/kg (i.p.) with each dose given prior to an acute (45min) locomotion test. Whereas PAL-287 is a potent releaser of serotonin, PAL-353 is not. Each drug induces comparable release of norepinephrine (NE) and of dopamine (DA). KEY FINDINGS: Control and lead rats exhibited minimal locomotion to PAL-287. PAL-353 produced a dose-dependent activation of locomotion in control rats relative to the effects of PAL-287 in control rats. Lead-exposed rats exhibited a subsensitivity to PAL-353 at doses of 4 and 8umol/kg. SIGNIFICANCE: The subsensitivity of lead rats to PAL-353 is consistent with a lead-induced diminution of dopamine function, an effect noted earlier for the reuptake inhibitor cocaine (Nation et al. 2000). The similar response of lead and control rats to PAL-287 is inconsistent with diminished serotonin function.
AIMS: The precise neurochemical perturbations through which perinatal (gestation/lactation) lead exposure modifies the reinforcement efficacy of various psychoactive drugs (e.g., cocaine, opiates) are unknown. The present study considers the role of altered serotonin and dopamine functionality in perinatal lead-psychostimulant interactions. MAIN METHODS: Female rats were administered a 16-mg lead or a control solution (p.o.) for 30days prior to breeding with non-exposed males. Lead exposure was discontinued at weaning (postnatal day [PND] 21). Starting at PND 120, male rats born to control or lead-exposed dams were injected with either PAL-287 or PAL-353, at doses of 0, 2, 4, 8, or 16umol/kg (i.p.) with each dose given prior to an acute (45min) locomotion test. Whereas PAL-287 is a potent releaser of serotonin, PAL-353 is not. Each drug induces comparable release of norepinephrine (NE) and of dopamine (DA). KEY FINDINGS: Control and lead rats exhibited minimal locomotion to PAL-287. PAL-353 produced a dose-dependent activation of locomotion in control rats relative to the effects of PAL-287 in control rats. Lead-exposed rats exhibited a subsensitivity to PAL-353 at doses of 4 and 8umol/kg. SIGNIFICANCE: The subsensitivity of lead rats to PAL-353 is consistent with a lead-induced diminution of dopamine function, an effect noted earlier for the reuptake inhibitor cocaine (Nation et al. 2000). The similar response of lead and control rats to PAL-287 is inconsistent with diminished serotonin function.
Authors: Paul J Wellman; Kristina W Davis; P Shane Clifford; Richard B Rothman; Bruce E Blough Journal: Drug Alcohol Depend Date: 2008-12-04 Impact factor: 4.492
Authors: Jack R Nation; Aaron L Cardon; Heather M Heard; Rodrigo Valles; Gerald R Bratton Journal: Psychopharmacology (Berl) Date: 2003-03-25 Impact factor: 4.530
Authors: Mellessa M Miller; Jenna L N Sprowles; Jason N Voeller; Abby E Meyer; Helen J K Sable Journal: Neurotoxicol Teratol Date: 2017-04-29 Impact factor: 3.763