Does paternal methamphetamine exposure affect the behavior of rat offspring during development and in adulthood?

Methamphetamine (MA) is one of the most abused psychostimulants in the Czech Republic and worldwide. Previous studies have demonstrated the adverse effects of maternal drug abuse. However, the father's contribution as a parent and donor of the half genetic information is unclear. The present study aimed to examine the effect of paternal MA exposure on behavioral development and locomotor activity in rat offspring. MA was administrated subcutaneously for 30 days at a dose of 5 mg/kg to adult male rats. The impact of paternal MA exposure on rat pups was investigated using behavioral tests during development and locomotor activity tests in adulthood. Prior to testing, adult offspring were exposed to an acute challenge dose of MA (1 mg/kg) to examine the possible sensitizing effect of the paternal treatment. Our results found no significant differences in behavioral development or locomotor activity in adulthood of offspring linked to paternal MA application. These results differ from the effects induced by maternal MA application. Further, our results demonstrated a significant increase in locomotor activity on the Laboras test after acute MA application. When comparing sex differences, females showed more activity than males in adulthood, whereas males were more active during development.

Can prenatal methamphetamine exposure be considered a good animal model for ADHD?

Attention-deficit/hyperactivity disorder (ADHD) is a mental disorder with a heterogeneous origin with a global incidence that continues to grow. Its causes and pathophysiological mechanisms are not fully understood. It includes a combination of persistent symptoms such as difficulty in concentration, hyperactivity and impulsive behavior. Maternal methamphetamine (MA) abuse is a serious problem worldwide, it can lead to behavioral changes in their offspring that have similarities with behavioral changes seen in children with ADHD. There are several types of ADHD animal models, e.g. genetic models, pharmacologically, chemically and exogenously induced models. One of the exogenously induced ADHD models is the hypoxia-induced model. Our studies, as well as those of others, have demonstrated that maternal MA exposure can lead to abnormalities in the placenta and umbilical cord that result in prenatal hypoxia as well as fetal malnutrition that can result in irreversible changes to experimental animals. Therefore, the aim the present study was to compare the cognitive impairments in MA exposure model with those in established model of ADHD - prenatal hypoxia model, to test whether MA exposure is a valid model of ADHD. Pregnant Wistar rats were divided into four groups based on their gestational exposure to MA: (1) daily subcutaneous injections of MA (5 mg/kg), (2) saline injections at the same time and volume, (3) daily 1-hr hypoxia (10 % O2), and (4) no gestational exposure (controls). Male rat offspring were tested for short-term memory in the Novel Object Recognition Test and the Object Location Test between postnatal days 35 and 40. Also their locomotor activity in both tests was measured. Based on the present results, it seems that prenatal MA exposure is not the best animal model for ADHD since it shows corresponding symptoms only in certain measures. Given our previous results supporting our hypothesis, more experiments are needed to further test possible use of prenatal MA exposure as an animal model of the ADHD.

Effect of methamphetamine exposure on sexual behavior and locomotor activity of adult male rats.

Drug addiction and its consequences on social life and behavior is currently a worldwide problem. Methamphetamine (MA) is one of the most abused psychostimulants in the Czech Republic. MA elevates mood, increases concentration, reduces appetite, and promotes weight loss. However, high doses and long-term abuse can induce psychosis, hallucinations, paranoia, violent behavior, and can lead to cardiovascular problems. Regarding its high prevalence and negative impact on health and social life, MA needs to be fully investigated. Previous studies have demonstrated the impairing effect of MA drug abuse on female behavior. However, MA's influence on male sexual behavior is not entirely clear. The aim of this study was to examine the effect of MA exposure on sexual behavior and spontaneous locomotor activity of adult male rats. MA was administrated subcutaneously at a dose of 5 mg/kg daily for a period of 30 days. The control group was exposed to saline (SA) at the same time and same volume. At the end of the application period, exposed male rats were paired with non-treated female rats, and their behavior was recorded for 2 h. Sexual mating behavior was described in terms of mounting frequency, intromission frequency, ejaculation frequency, sniffing time, intromission latency and the post-ejaculatory interval. Spontaneous locomotor activity in postnatally exposed male rats was studied using the Laboras apparatus. Acute doses of MA (1 mg/kg) or SA were administrated to probe the sensitizing effect of previous chronic MA exposure. Afterward, the animal was placed in an unknown environment and monitored for 1 h. Behavior was automatically evaluated using Laboras software by analyzing the following parameters: duration of locomotion (s), duration of immobility (s), rearing (vertical exploratory behavior), time spent grooming (s), average speed (mm/s), and distance traveled (m). Our results indicate that MA administration has a negligible effect on the sexual behavior of adult male rats. However, more experiments have to be performed to examine the influence of MA exposure on spermatogenesis and the behavior of offspring. Data from the Laboras test showed that MA exposure has a significant effect on locomotor activity in both acute as well as subchronic MA application. In conclusion, our results show that administration of MA in adult male rats does not affect sexual performance and motivation but does increase locomotor and exploratory activity in an unknown environment.

ADHD symptoms induced by prenatal methamphetamine exposure.

Methamphetamine is commonly used psychostimulant in the Czech Republic and is often abused by pregnant women. Methamphetamine may cause abnormalities in placenta and umbilical cord that results in hypoxia and malnutrition. ADHD is a mental disorder with a heterogeneous origin. The number of patients suffering from ADHD is growing. The pathophysiological mechanisms causing ADHD have not yet been clarified. There are very few rat models for ADHD and include genetic models, chemically induced models (ethanol, nicotine, PCBs, 6-hydroxydopamine lesion) or environmentally induced models (anoxia). The aim of the present study was to test prenatal methamphetamine exposure (5 mg/kg) as a potential novel animal model for ADHD. We found that adult male offspring prenatally exposed to methamphetamine presented hyperactivity while exploring novel environments. Together with cognition changes found in our previous studies, these might represent symptoms similar to those seen in ADHD. More experiments are planned to investigate our hypothesis.

What is the role of subcutaneous single injections on the behavior of adult male rats exposed to drugs?

Psychostimulants, as well as cannabinoids, have been shown to significantly affect a great variety of behaviors in both humans and laboratory animals. Our previous studies have repeatedly demonstrated that the application of the vehicle for psychostimulants, i.e. saline, to control groups, generated different behavioral test results compared to absolute naive controls (i.e. without any injection). Therefore, our present study has set three goals: (1) to evaluate the effect of three different psychostimulant drugs, (2) to evaluate the effect of three doses of delta 9-tetrahydrocannabinol (THC), and (3) to evaluate the effect of saline and ethanol injections vs sham injections and no injection on spontaneous behavior of adult male rats. The LABORAS test (Metris B.V., Netherlands) was used to examine spontaneous locomotor activity and exploratory behavior in an unknown environment over 1 h. In Experiment 1, psychostimulant drugs were tested: single subcutaneous (s.c.) injections of amphetamine (5 mg/kg), cocaine (5 mg/kg), and 3,4-methylenedioxymethamphetamine (MDMA) (5 mg/kg) were applied prior to testing. Control animals received the same volume (1 ml/kg) of s.c. saline. In Experiment 2, the effect of three doses of THC (1, 2, and 5 mg/kg, s.c.) were examined. An s.c. injection of vehicle (ethanol) was used as a control. In Experiment 3, injections of saline and ethanol were compared to the group receiving a sham s.c. injection and to a group of absolute "naive" controls. Our results demonstrated that (1) all psychostimulants increased locomotion time, distance traveled, and speed while decreasing immobility time of adult male rats relative to saline controls. The most prominent effect was associated with MDMA; (2) The effect of THC was dose-dependent and was most apparent within the first 10 min of the LABORAS test. (3) With regard to the effect of injection: absolute controls (without injection) compared to animals injected with ethanol, saline, or sham-injected displayed reduced immobility time, traveled longer distances, and had increased speed. In conclusion, our data showed drug dependent behavioral changes in adult male rats after application of psychostimulants and cannabinoids. Our findings also suggest that not only drugs but the actual single injection per se also affects the behavior of laboratory animals in an unknown environment. This effect seems to be associated with the acute stress associated with the injection.