Psychostimulants, including methamphetamine (MA), haveneurotoxic effect,
especially, if they are targeting CNS during its critical periods of development. The present study was aimed to examine cognitive changes after prenatal and neonatal MAtreatment in combination with chronic MA
exposure in adulthoodof male rats. Eight groups of male rats were tested in adulthood:males whose mothers were exposed to MA (5 mg/kg) or saline(SA, 1 ml/kg) during the first half of gestation period (GD 1-11),the second half of gestation period (GD 12-22) and neonatalperiod (PD 1-11). In addition, we compared indirect neonatalapplication via the breast milk
with the group of rat pups that received MA or SA directly by injection
(PD 1-11). Males weretested in adulthood for cognitive changes in the
Morris WaterMaze (MWM). MWM experiment lasted for 12 days: Learning(Day 1-6), Probe test (Day 8) and Retrieval Memory test
(Day 12). Each day of the MWM animals were injected with MA(1 mg/kg)
or SA (1 ml/kg). Prenatal MA exposure did not inducechanges in learning abilities of male rats, but neonatal exposureto MA leads to an increase search errorsand latencies to find thehidden platform. Prenatal and also
neonatal MA exposureimpaired cognitive ability to remember the position of the platform in Retrieval Memory test in adulthood. Animals exposed to the
prenatal treatment within the second half of gestation(ED 12-22) swam longer, slower and spent more time to find the hidden platform in Retrieval Memory test than animals exposedthroughout other periods. The present
study demonstrated thatstage of development is crucial for determination
the cognitivedeficits induced by prenatal or neonatal MA exposure.
The aim of the present study was to compare effect of three low doses of morphine (MOR) and delta9-tetrahydrocannabinol (THC) on social behavior tested in Social interaction test (SIT). 45 min prior to testing adult male rats received one of the drugs or solvents: MOR (1; 2.5; 5 mg/kg); saline as a solvent for MOR; THC (0.5; 1; 2 mg/kg); ethanol as a solvent for THC. Occurrence and time spent in specific patterns of social interactions (SI) and non-social activities (locomotion and rearing) was video-recorded
for 5 min and then analyzed. MOR in doses of 1 and 2.5 mg/kg
displayed decreased SI in total. Detailed analysis of specific patterns of SI revealed decrease in mutual sniffing and allo-grooming after all doses of MOR. The highest dose (5 mg/kg) of MOR decreased following and increased genital investigation. Rearing activity was increased by lower doses of MOR (1 and 2.5 mg/kg). THC, in each of the tested doses, did not induce any specific changes when compared to matching control group (ethanol). However, an additional statistical analysis showed differences between all THC groups and their
ethanol control group when compared to saline controls. There was lower SI in total, lower mutual sniffing and allo-grooming, but higher rearing in THC and ethanol groups than in saline control group. Thus, changes seen in THC and ethanol groups are seemed to be attributed mainly to the effect of the ethanol. Based on the present results we can assume that opioids affect SI more than cannabinoid.
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 naïve
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 “naïve” 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 dosedependent 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.