Sex differences in anxiety-like behavior and locomotor activity following prenatal and postnatal methamphetamine exposure in adult rats L. Hrubá, B. Schutová, R. Šlamberová ⁎ Charles University in Prague, Third Faculty of Medicine, Department of Normal, Pathological and Clinical Physiology, Prague, Czech Republic abstract article info Article history: Received 22 March 2011 Received in revised form 21 July 2011 Accepted 16 August 2011 Keywords: Methamphetamine Locomotion Exploratory behavior Anxiety Open field Elevated plus maze The aim of the present study was to investigate the impact of prenatal and postnatal methamphetamine (MA) exposure on behavior and anxiety in adult male and female rats. Mothers were daily exposed to injection of MA (5 mg/kg) or saline (S): prior to impregnation and throughout gestation and lactation periods. On postna- tal day 1, pups were cross-fostered so that each mother raised 6 saline-exposed pups and 6 MA-exposed pups. Based on the prenatal and postnatal exposure 4 experimental groups (S/S, S/MA, MA/S, MA/MA) were tested in the Open field (OF) and in the Elevated plus maze (EPM) in adulthood. Locomotion, exploration, immobility and comforting behavior were evaluated in the OF, while anxiety was assessed in the EPM. While prenatal MA exposure did not affect behavior and anxiety in adulthood, postnatal MA exposure (i.e. MA administration to lactating mothers) induced long-term changes. Specifically, adult female rats in diestrus and adult males post- natally exposed to MA via breast milk (S/MA and MA/MA) had decreased locomotion and exploratory behav- ior in the OF and showed increased anxiety-like behavior in the EPM when compared to female rats in diestrus or males postnatally exposed to saline (S/S and MA/S). In adult females in proestrus, postnatal exposure to MA affected only exploratory behavior in the OF when compared to rats in proestrus postnatally exposed to saline. Thus, the present study shows that postnatal exposure to MA via breast milk impairs behavior in unfamiliar environment and anxiety-like behavior of adult male and female rats more than prenatal MA exposure. © 2011 Elsevier Inc. All rights reserved. 1. Introduction Methamphetamine (MA) is a psychostimulant drug abuse of which represents a dominant problem in the Czech Republic and is one of the most widely abused “hard” drugs worldwide. The popularity of this drug seems to be due to its easy production, low cost, stimulatory effect and addictive properties [1,2]. Approximately half of MA users are women, mostly of reproductive age, and consequently some of them become pregnant while using the drug [3]. MA crosses the placental and hematoencephalic barrier easily [4] and therefore it may affect the development of the fetus. There are studies suggesting that MA exposure during pregnancy can impair the development of the neonatal central nervous system [5,6]. Smith et al. [7] showed decreased arousal, increased stress and poor quality of movement in prenatally MA- exposed neonates. Another study demonstrated altered neonatal behavioral patterns characterized by abnormal sleep, poor feeding, tremors, and hypertonia as well as visual and motor difficulties in neonates exposed to MA during the prenatal period [8]. Lactating neonates can be exposed to MA also postnatally since amphetamines are concentrated and secreted in mother's breast milk [9]. Experimental studies show that psychostimulants seriously affect behavior and anxiety. Specifically, psychostimulants induce aggres- sive behavior, cause changes in social interactions [10–12] and have anxiogenic effect [13–15]. Other studies suggest that there are sex dif- ferences in response to MA in behaviors, which are mediated via cen- tral dopaminergic pathways, such as locomotion, rearing and sniffing [16]. Female rats were shown to be more sensitive to the locomotor activating effect of MA (0.1–3.0 mg/kg) than male rats [17]. A similar effect has been observed in other psychomotor stimulants, including cocaine and amphetamine [18,19]. Moreover, there are studies show- ing sex differences in rat brain of serotoninergic [20] and dopaminer- gic [21] systems, while other authors found no changes in these systems [22]. Note, that serotoninergic and dopaminergic systems are both involved in the mechanism of action of all the psychostimu- lant drugs [23,24]. With regard to relationship among MA, sex differ- ences and monoamine system was found that male mice show significantly greater nigrostriatal dopaminergic neurotoxicity to MA than females [25]. The design used in our studies is supposed to partially simulate the exposure in infants of drug abusing women. In other words dams are administered the drugs not only during gestation but also before this period and also during the lactation period. Because drug abusing human mothers do not inject drug to their children, but to themselves, and therefore their children are exposed to the effects of the drug during lactation indirectly via breast milk, we do the same in rats. Our previous Physiology & Behavior 105 (2012) 364–370 ⁎ Corresponding author at: Department of Normal, Pathological and Clinical Physiology, Ke Karlovu 4, 12000 Prague 2, Czech Republic. Tel.: +420 224902713; fax: +420 224902750. E-mail address: rslamber@lf3.cuni.cz (R. Šlamberová). 0031-9384/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.physbeh.2011.08.016 Contents lists available at SciVerse ScienceDirect Physiology & Behavior journal homepage: www.elsevier.com/locate/phb