title: In utero methanesulfonyl fluoride differentially affects learning and maze performance in the absence of long-lasting cholinergic changes in the adult rat.
abstract: There is increasing evidence that acetylcholinesterase (AChE) may have various specific developmental roles in brain development. Nevertheless, specific effects of AChE inhibition during early brain development have not been adequately described. Therefore, methanesulfonyl fluoride (MSF), an irreversible AChE inhibitor that shows high selectivity for the CNS was used to produce AChE inhibition in utero to study subsequent adult behaviors, sleep, and cholinergic markers. Rats exposed to MSF in utero showed a deficit in spatial learning tasks using appetitive motivation but, surprisingly, they performed equally well or better than controls when aversive motivation was used. One hypothesis was that MSF treatment in utero affected the response to stress. Tests of anxiety however showed no differences in basal levels of anxiety. Studies of sleep behavior, however, indicated a higher level of REM sleep which is only seen during the light phase of male rats exposed to MSF in utero as compared to controls. No differences in cholinergic markers in the brains of adults were found except that females exposed to MSF in utero had a higher level of ChAT activity in the synaptosomal fraction of the hippocampus. Even so, whether cholinergic alterations accompany the in utero MSF exposure remains to be determined. The failure to find widespread changes in cholinergic markers in the adult brains suggests changes in behaviors should be further investigated by testing the participation of postsynaptic mechanisms, measuring of cholinergic markers during earlier development periods and the possible participation of other neurotransmitter systems to clearly reveal the role of the cholinergic system following in utero MSF exposure.
authors.affiliation: University of Texas at El Paso, Department of Biology, 500 West University Avenue, El Paso, Texas 79968, USA. lmcarcoba@gmail.com
authors.forename: Luis M
authors.initials: LM
authors.lastname: Carcoba
authors.forename: Miguel
authors.initials: M
authors.lastname: Santiago
authors.forename: Donald E
authors.initials: DE
authors.lastname: Moss
authors.forename: Rafael
authors.initials: R
authors.lastname: Cabeza
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood; D000818:Animals; D001007:Anxiety / Q000523:psychology; D002794:Choline / Q000097:blood; D002795:Choline O-Acetyltransferase / Q000097:blood; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000523:psychology*; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects; D012895:Sleep, REM / Q000187:drug effects; D013028:Space Perception / Q000187:drug effects; D013450:Sulfones / Q000494:pharmacology*; D013550:Swimming / Q000523:psychology
chemical_list: D002800:Cholinesterase Inhibitors; D013450:Sulfones; C005109:methanesulfonyl fluoride; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D002794:Choline