Does Prenatal Methamphetamine Exposure Induce Cross-sensitization to Cocaine and Morphine in Adult Male Rats? 190)

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

Impact of Methamphetamine Administered Prenatally and in Adulthood on Cognitive Functions of Male Rats Tested in Morris Water Maze

Abstract: Studies showed that stimulant drugs that affect the monoaminergic system alter both behavioral and cognitive processes. The aim of the present study was to investigate the impact of prenatal and acute methamphetamine (MA) exposure on cognitive functions of adult male rats tested in Morris water maze (MWM). We tested adult male rats prenatally exposed to MA (5 mg/kg), saline or no injection. Half of the animals were injected daily with MA (1 mg/kg) after finishing the testing. All injections were administered subcutaneously. Three types of tests were used: (1) "Place navigation test" (Learning), (2) "Probe test" (Probe) and (3) "Retention memory test" (Memory). Our results showed that prenatal MA exposure did not affect the test of learning and the Probe test. In the test of memory prenatally MA-exposed rats had lower latencies than animals prenatally exposed to saline. Further, acute MA administration increased the speed of swimming in all rats regardless of prenatal drug exposure and the type of test and, however, the increase in the speed was significantly greater in rats prenatally exposed to MA than in rats without any prenatal exposure. In addition, acute MA application significantly prolonged trajectories in the Place navigation test. The present study thus demonstrates that: (1) Prenatal MA exposure does not affect learning in the MWM. (2) Prenatal MA exposure increases the sensitivity to acute drug injection. (3) Acute MA application impairs learning in the MWM

Does Prenatal Methamphetamine Exposure Induce Cross-sensitization to Cocaine and Morphine in Adult Male Rats?

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 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

Reductions in Frontocortical Cytokine Levels are Associated with Long-Lasting Alterations in Reward Valuation after Methamphetamine

Alterations in reward valuation are thought to have a central role at all stages of the addiction process. We previously reported work aversion in an effortful T-maze task following a binge exposure to methamphetamine, and no such changes in effort following escalating doses. Limitations of the T-maze task include its two available options, with an effort requirement, in the form of increasing barrier height, varying incrementally as a function of time, and reward magnitudes held constant. Reward preferences and choices, however, are likely affected by the number of options available and the manner in which alternatives are presented. In the present experiment, we investigated the long-lasting, off-drug effects of methamphetamine on reward choices in a novel effortful maze task with three possible courses of action, each associated with different effort requirements and reward magnitudes. Neuroinflammatory responses associated with drug exposure, proposed as one of the mechanisms contributing to suboptimal choices on effort-based tasks, were also examined. We investigated region-specific changes in pro- and anti-inflammatory markers in the mesocorticolimbic pathway after methamphetamine, and their relationship with animals' reward choices. We observed long-lasting, increased sensitivity to differences in reward magnitude in the methamphetamine group: animals were more likely to overcome greater effort costs to obtain larger rewards on our novel effortful maze task. These behavioral changes were strongly predicted by pronounced decreases in frontocortical cytokines, but not amygdalar or striatal markers. The present results provide the first evidence that neuroinflammatory processes are associated with alterations in reward valuation during protracted drug withdrawal

Developmental and behavioral consequences of prenatal methamphetamine exposure: A review of the Infant Development, Environment, and Lifestyle (IDEAL) study

This study reviews the findings from the Infant Development, Environment, and Lifestyle Study (IDEAL), a multisite, longitudinal, prospective study designed to determine maternal outcome and child growth and developmental findings following prenatal methamphetamine exposure from birth up to age 7.5 years. These findings are presented in the context of the home environment and caregiver characteristics to determine how the drug and the environment interact to affect the outcome of these children. No neonatal abstinence syndrome requiring pharmacologic intervention was observed but heavy drug exposure was associated with increased stress responses in the neonatal period. Poorer inhibitory control was also observed in heavy methamphetamine exposed children placing them at high risk for impaired executive function. Independent of methamphetamine exposure, children with more responsive home environments to developmental and emotional needs demonstrated lower risks for internalizing and externalizing behavior