Prenatal methamphetamine exposure affects the mesolimbic dopaminergic system and behavior in adult offspring.
Methamphetamine is a commonly abused psychostimulant that causes addiction and is often abused by pregnant women. Acute or chronic administration of methamphetamine elevates the levels of the extracellular monoamine neurotransmitters, such as dopamine. The aim of the present study was to show whether prenatal exposure to methamphetamine (5mg/kg, entire gestation) or saline in Wistar rats induces changes in dopamine levels and its metabolites in the nucleus accumbens, and in behavior (locomotor activity, rearing, and immobility) after the administration of a challenge dose of methamphetamine (1mg/kg) or saline in male offspring. We found that adult offspring prenatally exposed to methamphetamine had higher basal levels of dopamine (about 288%), dihydroxyphenylacetic acid (about 67%) and homovanillic acid (about 74%) in nucleus accumbens. An increased basal level of dopamine corresponds to lower basal immobility in offspring prenatally exposed to methamphetamine. The acute injection of methamphetamine in adulthood increased the level of dopamine in the nucleus accumbens, which is related to an increase of locomotion and rearing (exploration). In addition, prenatally methamphetamine-exposed rats showed higher response to the challenge dose of methamphetamine, when compared to prenatally saline-exposed rats. In conclusion, rats exposed to methamphetamine in utero have shown changes in the mesolimbic dopaminergic system and were more sensitive to the administration of the acute dose of methamphetamine in adulthood.
Bubenikova-Valesova
Vera
V
Prague Psychiatric Center, Department of Biochemistry and Brain Pathophysiology, Ustavní 91, 181 03 Prague 8, Bohnice, Czech Republic. bubenikova@pcp.lf3.cuni.cz
Kacer
Petr
P
Syslova
Kamila
K
Rambousek
Lukas
L
Janovsky
Martin
M
Schutova
Barbora
B
Hruba
Lenka
L
Slamberova
Romana
R
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D018759:Adrenergic Uptake Inhibitors / Q000633:toxicity; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000254:growth & development / Q000503:physiopathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D013995:Time; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology
D018759:Adrenergic Uptake Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D008694:Methamphetamine; D004298:Dopamine; D006719:Homovanillic Acid