Prenatal exposure to methamphetamine (METH) increases nociceptive sensitivity in adult rats. As the strong analgesics have high abuse potential and drugs of abuse are known to have analgesic properties, the aim was to study analgesic effect of different psychostimulants in control and prenatally METHexposed rats. Latencies of withdrawal reflexes of hind limbs and the tail on thermal nociceptive stimuli were repeatedly measured in 15-min intervals after the application of 5 mg/kg s.c. of amphetamine (AMPH), methamphetamine (METH), cocaine (COC), 3,4-methylenedioxymethamphetamine (MDMA) or morphine (MOR). In all groups, AMPH induced on hind limbs stronger analgesia than METH and MDMA whereas COC and MOR were practically without any effect. On the tail, effect of AMPH did not differ from that of MOR. All psychostimulants increased defecation in comparison with MOR and in all groups the number of defecation boluses positively correlated with analgesia of the hind limbs. We did not confirm that prenatal exposure to METH makes adult rats more sensitive either to same drug or to other psychostimulants. The different analgesic potencies of psychostimulants and MOR at different body sites indicate the possible existence of a somatotopic organization of pain inhibition, which is controlled by different mechanisms., A. Yamamotová, R. Šlamberová., and Obsahuje seznam literatury
Drug abuse of pregnant women is a growing problem. The effect of prenatal drug exposure may have devastating effect on development of the offsprings that may be long-term or even permanent. One of the most common drug abused by pregnant women is methamphetamine (MA), which is also the most frequently abused illicit drug in the Czech Republic. Our previous studies demonstrated that prenatal MA exposure alters behavior, cognition, pain and seizures in adult rats in sex-specific manner. Our most recent studies demonstrate that prenatal MA exposure makes adult rats more sensitive to acute injection of the same or related drugs than their controls. The aim of the present study was to examine the effect of prenatal MA exposure on drugseeking behavior of adult male rats tested in the Conditioned place preference (CPP). Adult male rats were divided to: prenatally MA-exposed (5 mg/kg daily for the entire prenatal period), prenatally saline-exposed (1 ml/kg of physiological saline) and controls (without maternal injections). The following drugs were used in the CPP test in adulthood: MA (5 mg/kg), amphetamine (5 mg/kg), cocaine (5 and 10 mg/kg), morphine (5 mg/kg), MDMA (5 mg/kg) and THC (2 mg/kg). Our data demonstrated that prenatally MA-exposed rats displayed higher amphetamine-seeking behavior than both controls. MA as well as morphine induced drug-seeking behavior of adult male rats, however this effect did not differ based on the prenatal MA exposure. In contrast, prenatal MA exposure induced rather tolerance to cocaine than sensitization after the conditioning in the CPP. MDMA and THC did not induce significant effects. Even though the present data did not fully confirmed our hypotheses, future studies are planned to test the drug-seeking behavior also in self-administration test., R. Šlamberová, ... [et al.]., and Obsahuje seznam literatury
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 metham phetamine (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 pr enatal 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., R. Šlamberová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
There is growing evidence that methamphetamine use during pregnancy may produce detrimental cardiovascular effects in the adult offspring. Prior work demonstrated that chronic methamphetamine exposure throughout the gestational period causes adult female offspring to become hypersensitive to myocardial ischemic injury. The goal of the present study was to determine whether this methamphetamine-induced effect occurs early or late in the gestational period. Pregnant female rats were divided into 4 experimental groups. Groups 1 and 2 received subcutaneous injections of saline (group 1) or methamphetamine (5 mg/kg) (group 2) throughout the gestational period. Group 3 received methamphetamine injections on days 1-11 and saline on days 12-22, and group 4 received saline on days 1-11 and methamphetamine on days 12-22. Hearts were isolated from adult (8 weeks) female offspring and subjected to 30 min ischemia and 2 hours reperfusion on a Langendorff isolated heart apparatus. Contractile function was measured via an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Infarcts were significantly larger in methamphetamine exposed offspring regardless of whether they had been exposed to methamphetamine during the first half or the second half of the gestational period. Prenatal exposure to methamphetamine had no effect on preischemic contractile function or postischemic recovery of contractile function. These data indicate that methamphetamine use during either the first half or second half of pregnancy increases susceptibility to myocardial infarction in adult female offspring. These data provide further evidence that prenatal exposure to methamphetamine may increase the risk of developing cardiovascular diseases during adulthood.