Social behavior involves complex of different forms of interactions between individuals that is essential for
healthy mental and physical development throughout lifespan. Psychostimulants, including methamphetamine
(MA), have neurotoxic effect, especially, if they are targeting CNS during its critical periods of development. The
present study was aimed on evaluation of changes in social interactions (SI) following scheduled prenatal/
neonatal MA treatment in combination with acute application in adulthood. Eight groups of male and eight
groups of female rats were tested in adulthood: rats, whose mothers were exposed to MA (5 mg/ml/kg) or saline
(SA, 1 ml/kg) during the first half of gestation (ED 1–11), the second half of gestation (ED 12–22) and neonatal
period (PD 1–11). To do this, we compared indirect neonatal applications via the exposed dams with group of rat
pups that received MA or SA directly through injections. In adulthood, half animals from each group were
injected with MA (1 mg/kg), second half with saline 45 min prior to the Social Interaction Test. Females and
males were observed for social and nonsocial activities of two unfamiliar individuals of the same sex and
treatment in a familiar Open field arena. The present study demonstrated that prenatal/neonatal MA exposure
leads to decrease the time spent in genital investigation, following and nonsocial activity. Acute dose of MA leads
to a decrease in all SI patterns and to an increase in nonsocial activities relative to acute SA. Females were more
active than males. Animals exposed to prenatal/neonatal treatment during the second half of gestation (ED
12–22) and throughout lactation period (PD 1–11 indirect/direct) had fewer SI and greater exploratory behavior
than animals exposed during the first half of gestation (ED 1–11).

In the present study we investigated the sex differences in the effect of adult long-term drug treatment
on cognitive functions of Wistar rats, which were prenatally exposed to MA (5 mg/kg) or saline.
Cognitive functions were tested as an ability of spatial learning in the Morris Water Maze (MWM),
which consisted of three types of tests: “Place Navigation Test”; “Probe Test”, and “Memory Recall
Test”. Adult animals were injected daily, after completion of the last trial, either with saline or cocaine
(COC; 5 mg/kg), MDMA (3,4-methylenedioxy-methamphetamine; 5 mg/kg), morphine (MOR; 5 mg/kg),
or delta-9-tetrahydrocannabinol (THC; 2 mg/kg). Results revealed worsened MWM performance in
female rats after drug treatment in adulthood. Not only were traditionally investigated parameters
affected by drug treatment (latency of platform acquisition, search strategy, distance traveled), but also
strategies used by animals (thigmotaxis, scanning). Analyses of search strategies observed in the Place
Navigation Test, as well as in the Memory Recall Test, demonstrated variations in the percentage of time
spent in thigmotaxis and scanning in females after treatment with COC, MDMA, MOR, and THC. Although
we did not see a sensitizing effect of prenatal MA, in some cases the effect of drug treatment in adulthood
differed depending on the prenatal drug exposure. The data presented in this study demonstrates that
exposure to drugs with various mechanisms of action alters spatial abilities of female rats in the MWM.
Alterations in the effect of adult drug treatment with reference to prenatal drug exposure were also found
in the present study.