Background: Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent neuropsychiatric disorders with morphological brain abnormalities. There is a growing body of evidence that abnormalities in the dopaminergic system may account for ADHD pathogenesis. However, it is not clear whether the dopaminergic system is hyper or hypoactive. To determine whether the DA neurons and/or axons deficiency might be the cause of the postulated dopaminergic hypofunction in spontaneously hypertensive rats (SHR, animal model of ADHD), this study examined the dopaminergic neurons and fibers in the brain tissues of SHRs and Wistar Kyoto rats (WKY, control animals). Here, we performed immunohistochemical tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) staining on brain sections collected on juveniles from SHR and WKY. Moreover, behavioral testing to examine the hyperactivity in the open field area was also elucidated. Results: The mesocortical dopaminergic system appears to be normal in juvenile SHR, as suggested by (i) no alteration in the area density of TH-immunoreactive (TH-ir) dopaminergic neurons in the ventral tegmental area (VTA), (ii) no alterations in the volume density of TH-ir fibers in layer I of the prelimbic (PrL) subregion of medial PFC (mPFC), (iii) no alteration in the percentage of TH-ir dopaminergic fibers in layer I of the PrL subregion of mPFC as revealed by TH and/or DBH immunoreactivity. Furthermore, the SHR showed increased locomotor activity than WKY in the open field test. Conclusions The demonstration of no alteration in mesocortical dopaminergic neurons and fiber in SHR raises some concern about the position of SHR as an animal model of the inattentive subtype of ADHD. However, these results strengthen this strain as an animal model of hyperactive/impulsive subtype ADHD for future studies that may elucidate the underlying mechanism mediating hyperactivity and test various treatment strategies.

INTRODUCTIONThe hippocampus is an important region of the brain that regulates cognitive and emotional functions. In this study, we examined the impact of perinatal administration of testosterone propionate (TP) on the number of pyramidal neurons in the CA1 and CA3 regions of the hippocampi of female rats.

METHODSFive groups of rats were used in this study. Three groups of female rats were administered TP in either both the prenatal and the postnatal periods (Group 1), only the prenatal period (Group 2) or only the postnatal period (Group 3). The other two groups of rats included control females (Group 4) and control males (Group 5). The rats were sacrificed on postnatal Day 120 and their brains were analysed for hippocampal pyramidal neuron number using stereological methods.

RESULTSControl male rats (Group 5; p = 0.043) and TP-treated female rats in Groups 1 (p = 0.012) and 2 (p = 0.037), but not Group 3 (p > 0.05), had a significantly higher number of pyramidal neurons than control female rats (Group 4). The rats in Group 1 had the highest number of pyramidal neurons among the female rats.

CONCLUSIONPerinatal TP treatment has an augmenting effect on the number of pyramidal neurons in the hippocampi of female rats. We also found gender-based differences in the hippocampi of male and female rats, with a higher number of pyramidal neurons seen in male rats. Continuous TP administration during the prenatal and postnatal periods is more effective than administration only in the prenatal or postnatal period.

Animals ; Body Weight ; Female ; Hippocampus ; cytology ; drug effects ; Male ; Maternal Exposure ; Neurons ; drug effects ; Pregnancy ; Pregnancy, Animal ; Prenatal Exposure Delayed Effects ; Pyramidal Cells ; drug effects ; Rats ; Rats, Wistar ; Testosterone Propionate ; pharmacology