Behavioral alterations in adolescent and adult rats caused by a brief subtoxic exposure to chlorpyrifos during neurulation

Persistent cognitive alterations in rats after early postnatal exposure to low doses of the organophosphate pesticide, diazinon

“…1, weeks 4-5), rats exposed to either dose of DZN showed a significant reduction in response latency in early trials, just as seen previously with CPF [9,14], In contrast, the percent of spontaneous alternation was not significantly affected by DZN treatment. The controls averaged 84.6±8.7%, the 0.5 mg/kg/d DZN group 86.0±8.4% and the 2 mg/kg/d DZN group 86.1±7.9% alternation.…”

“…For a number of the observations, the behavioral impairments were similar to those identified in our previous work with CPF when exposure occurred either gestationally or postnatally [2,9,14,15]. There were also notable differences in the effect of the two agents, which might be expected.…”

“…Similar results were observed in rats exposed to CPF in early or late gestational periods [9,14], but not after CPF exposure in the early postnatal period [15]. Accordingly, the actions of the two OPs may be similar, but the critical periods over which each exerts the corresponding changes in neural function can be different.…”

“…Furthermore, these are translated into differences in the expression of specific proteins associated with cholinergic and serotonergic synapses [10,[22][23][24][25]. In the current study, we evaluated the neurobehavioral consequences of early neonatal DZN exposure using cognitive testing guidelines adapted from our earlier work on CPF [2,9,14,15]. In this case, we evaluated two doses of DZN subthreshold for producing clinical signs of acute toxicity, which were administered daily to neonatal rats on postnatal days (PND) 1-4.…”

Comparative developmental neurotoxicity of organophosphates in vivo: Transcriptional responses of pathways for brain cell development, cell signaling, cytotoxicity and neurotransmitter systems

“…The major effect shared by both CPF and DZN was a suppression of the development of ACh systems and promotion of monoamine systems, results at the transcriptional level that confirm earlier work on the switching of neuronal phenotype as a final outcome [4][5][6]25,49]. A change in transmitter phenotype is likely to produce "miswiring" of major brain circuits, where presynaptic neurons of one phenotype are juxtaposed to postsynaptic cells containing the incorrect complement of receptors and signaling pathways, effects that have already been noted as a final outcome for both ACh and 5HT systems [3,4,48,59,60]. Superimposed on these alterations, we found specific targeting of nAChR subtypes, a likely consequence of direct interaction of organophosphates with these ion channel receptors, as well as prominent effects on the receptors for the various monoamine neurotransmitters.…”