Faculty Collaboration Database

Waterborne lead exposure affects brain endocannabinoid content in male but not female fathead minnows (Pimephales promelas). Neurotoxicology 2005 Jan;26(1):9-15

Date

11/06/2004

Pubmed ID

15527869

DOI

10.1016/j.neuro.2004.08.001

Scopus ID

2-s2.0-7444252224 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

There are several similarities between the behavioral and neurochemical effects of lead (Pb2+) and the cannabinoids. Both Pb2+ exposure and cannabinoid treatment decrease exploratory behavior. Pb2+-induced hyperactivity has been observed in rats and fish. By comparison, cannabinoids increase locomotor activity at higher doses in rats. Moreover, Pb2+ exposure produces learning and memory impairments as do the cannabinoids. Many of the behavioral effects of Pb2+ are thought to be due, in part, to the ability of Pb2+ to either inhibit or mimic the actions of calcium (Ca2+). At low concentrations, Pb2+ enhances basal release of neurotransmitter from presynaptic terminals by increasing intracellular free Ca2+ concentrations. Pb2+ also decreases evoked neurotransmitter release due to blockade of voltage-gated Ca2+ channels. Interestingly, the endocannabinoids (eCBs) including N-arachidonylethanolamine (AEA) and 2-arachidonylglycerol (2-AG) are synthesized in response to increases in intracellular Ca2+ and activate the CB1 receptor that inhibits voltage-gated Ca2+ channels. We tested the hypothesis that waterborne Pb2+ exposure significantly affects whole-brain eCB content in adult male and female fathead minnows (Pimephales promelas). Waterborne Pb2+ exposure (1.0 ppm) resulted in a time-dependent accumulation of Pb2+ in bone in both males and females. Brain AEA and 2-AG content were significantly greater in females compared to males. Pb2+ exposure increased brain AEA content in males at 7 and 14 days of exposure and increased brain 2-AG content at 14 days. Pb2+ exposure had no effect on either brain AEA or 2-AG content in females at any of the time points examined. As eCBs serve as activity-dependent retrograde inhibitors of neurotransmitter release, the increase in brain eCB content would accentuate Pb2+-induced decreases in evoked neurotransmitter release in male but not female fathead minnows.

Author List

Rademacher DJ, Weber DN, Hillard CJ

Author

Cecilia J. Hillard PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Arachidonic Acids
Bone and Bones
Brain Chemistry
Cannabinoid Receptor Modulators
Chromatography, Liquid
Cyprinidae
Endocannabinoids
Female
Glycerides
Lead
Male
Mass Spectrometry
Sex Characteristics
Water Pollutants, Chemical