Information on the thesis

Organophosphorus compounds (OPs) are widely used in industry and
agriculture. Due to their high toxicity, their use is legislatively limited in many
countries.
The dissertation reveals the effects of one of the most common
organophosphorus insecticides – chlorpyrifos (CPF) on neurobehavioral parameters
of laboratory rats, in particular on their level of anxiety, research activity, short –
term and long – term memory. Changes in the above mentioned indicators were
studied both in adult female intoxicated rats (under conditions of acute and chronic
administration) and in their offspring. The scientific novelty of the work consists in
the study of neurobehavioral features of the second generation of rats, e.g. offspring
derived from intoxicated females, which, in turn, had no direct influence of the CRF
either during gestation or during postnatal development until adulthood. Their
parameters were compared with the behavior of both intact rats of the same age and
animals prenatally intoxicated with CPF. We also studied certain biochemical
(acetylcholinesterase, aspartate and alanine aminotransferase activity, alkaline
phosphatase and some other enzymes, total protein content) and hematological
parameters of rat blood.
The studies were carried out on white laboratory rats of the Vistar line of both
sexes. In total, 100 animals were used at all stages of the dissertation study. The
experimental comparison of the two commonly used modifications of the “Open field
test” array (round and square) did not reveal any significant differences in the main
informative parameters of the method, which made it possible to conclude that both
modifications can be used equally for rat behavior studies.
During chronic intoxication of adult female rats with 5, 10 and 15 mg/kg CPF
(daily for 30 days), there were no significant persistent changes in their behavior:
though the general anxiety of the intoxicated animals increased at the beginning of
exposure, eventually all indicators have normalized. However, in the offspring of
these intoxicated animals (most commonly in the group exposed to 15 mg/kg CPF)
we found statistically significant neurobehavioral deviations: excessive motor activity
and abnormally low duration and number of freezing. In general, the behavior of this
group of rats resembled manifestations of the hyperactivity syndrome. In addition,
significantly less rats of this group, compared to control, reached adulthood; the
Ketle’s coefficient was also lower. In contrast, in animals that were prenatally
intoxicated with 30 mg/kg CPF at 6– 7 gestation day, there was some deterioration in
their memory, but no signs of hyperactivity.
A single exposure to 15, 30 and 60 mg/kg CPF of adult female rats caused a
decrease in activity of AChE and increased the alkaline phosphatase activity, but did
not lead to significant changes in their behavior. In the offspring of these females,
conceived at 10 days after intoxication, signs of increased anxiety in low– stress
conditions (the placement of animals in an unknown territory), as well as an
abnormal reaction to moderate stress caused by bright light, were revealed. In
response to acute stress (drowning in water), no significant differences between the
experimental and control groups of animals were found.
Summarizing the data obtained in the work, we should confirm the presence of
the effects of intoxication even at low doses of CPF on the functional state of the
CNS of exposed animals, as well as their offspring conceived after the completion of
the exposure. In particular, in the offspring of females intoxicated with CPF,
behavioral tests showed signs of hyperactivity. Mechanisms of such effects of the
CPF on the behavior of the second generation need further study.
Keywords: chlorpyrifos, behavior, rats, anxiety, hyperactivity, behavioral tests,
neurobehavioral disorders, offspring.