The aim of this study was to investigate the effect of prenatal methamphetamine (MA) exposure and application of the same drug in adulthood on cognitive functions of adult female rats. Animals were prenatally exposed to MA (5 mg/kg) or saline (control group). The cognitive function was tested as ability of spatial learning in the Morris Water Maze (MWM). Each day of the experiment animals received an injection of MA (1 mg/kg) or saline. Our results demonstrated that prenatal MA exposure did not affect the latency to reach the hidden platform or the distance traveled during the Place Navigation Test; however, the speed of swimming was increased in prenatally MA-exposed rats compared to controls regardless of the treatment in adulthood. MA treatment in adulthood increased the latency and distance when compared to controls regardless of the prenatal exposure. Neither prenatal exposure, nor treatment in adulthood affected memory retrieval. As far as the estrous cycle is concerned, our results showed that prenatally MA-exposed females in proestrus/estrus swam faster than females in diestrus. This effect of estrous cycle was not apparent in control females. In conclusion, our results indicate that postnatal, but not prenatal exposure to MA affects learning of adult female rats.

R e c e i ve d Fe b r u a r y 2 3 , 2 0 1 2 ; A c c e p t e d Ju n e 2 5 , 2 0 1 2 .Key words: Anxiety -Behavior -Elevated plus-maze -Methamphetamine Abstract: Methamphetamines (MA) are psychostimulant drugs that are known to change individuals' behavior. Psychostimulants could either evoke positive emotions (e.g. joy and happiness) or attenuate negative emotional states (e.g. anxiety and depression) in humans. In animal experiments, the test of elevated plus-maze (EPM) is widely used. This test is appropriate for evaluation of anxiolytic and anxiogenic drug effects, or for examination of specific subtypes of anxiety disorders. The aim of the present study was to examine the effect of acute single dose of MA (1 mg/kg) on the behavior of laboratory rat in the EPM. The detailed ethologic analysis of behavior was performed using a modified protocol based on the study of Fernández Espejo (1997). Our results demonstrated that MA affects rat's behavior in the EPM in the majority of analyzed categories. The present protocol allowed us to determine positive anxiogenic effect of MA.

R e c e i ve d J a n u a r y 2 3 , 2 0 12 ; A c c e p t e d Ju n e 2 5 , 2 0 1 2 .Key words: Prenatal drug exposure -Methamphetamine -Cocaine -MorphineOpen field -Plantar test -Conditioned place preference -LocomotionNociception -Drug-seeking behavior Abstract:The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA) exposure to challenge dose of cocaine or morphine. Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male offspring (prenatally MA-or saline-exposed) were divided to groups with challenge doses of saline (1 ml/kg), cocaine (5 mg/kg) or morphine (5 mg/kg). Behavior in unknown environment was examined in Laboras, nociception in Plantar test, and active drug-seeking behavior in conditioned place preference (CPP). Our data demonstrate that cocaine increased the exploratory activity in Laboras test in prenatally saline-exposed, but decreased it in prenatally MA-exposed rats. An analgesic effect of cocaine was demonstrated only by the tail withdrawal and it was independent of the prenatal drug exposure. CPP test showed that prenatal MA exposure induced rather tolerance than sensitization to cocaine. In contrast to cocaine effects, morphine decreased rearing activity in both, prenatally MA-exposed and saline-exposed rats, and locomotion only in prenatally MA-exposed rats in the Laboras. In the Plantar Prague Medical Report / Vol. 113 (2012) No. 3, p. 189-205 test, the results demonstrated that morphine had an analgesic effect in prenatally saline-exposed rats but this effect was suppressed in prenatally MA-exposed rats. In the CPP test morphine induced drug-seeking behavior, which however was not affected by prenatal drug exposure. Thus, our data demonstrate that there is a cross-effect between prenatal MA exposure and the challenge dose of other drug in adulthood, however drug-seeking behavior is not increased by prenatal MA exposure as we expected.

The aim of the present study was to compare the response to acute application of several drugs in adult male and female rats prenatally exposed to methamphetamine (MA). Spontaneous locomotor activity and exploratory behavior of adult male and female rats prenatally exposed to MA (5 mg/kg) or saline were tested in a Laboras apparatus (Metris B.V., Netherlands) for 1 h. Challenge dose of the examined drug [amphetamine – 5 mg/kg; cocaine – 5mg/kg; MDMA (3,4-methylenedioxymethamphetamine) – 5 mg/kg; morphine – 5 mg/kg; THC (delta9-tetrahydrocannabinol) – 2 mg/kg] or saline was injected prior to testing. Our data demonstrate that prenatal MA exposure did not affect behavior in male rats with cocaine or morphine treatment, but increased locomotion and exploration in females. Application of amphetamine and MDMA in adulthood increased activity in both sexes, while cocaine and THC only in female rats. Morphine, on the other hand, decreased the activity in the Laboras test in both sexes. As far as sex and estrous cycle is concerned, the present study shows that males were generally less active than females and also females in proestrus-estrus phase of the estrous cycle were more active than females in diestrus. In conclusion, the present study shows that the prenatal MA exposure does not induce general sensitization but affects the sensitivity to drugs dependently to mechanism of drug action and with respect to gonadal hormones.