The uterine environment enhances cognitive competence.

Genetically identical mouse embryos were transferred into same-strain uteri (transfer controls) or into hybrid uteri. A third group was not transferred. When adult, the mice were given a series of behavioral tests. In-strain transfer controls differed from non-transfer mice only on two activity measures, and did not differ on any cognitive variable. In contrast, mice reared in hybrid uteri were found to be superior to in-strain transfer mice on discrimination learning, Lashley maze learning and Morris maze learning; they also showed better adaptation in an avoidance learning shuttlebox. To our knowledge this is the first study showing that the uterine environment can have a general enhancing effect upon cognitive competence across a broad range of behaviors

Effects of the non-pseudoautosomal region of the Y-chromosome on behavior in female offspring of two congenic strains of mice.

The learning behavior of female offspring of two strains of mice congenic for the Y-chromosome, BXSX/MpJ-Yaa and BXSB/MpJ-Yaa+, was examined. Significant differences were found in the Morris water maze and the Lashley III maze, demonstrating that the fathers\u27 Y-chromosome can indirectly affect their daughters\u27 behavior. Approximately half the mice had neocortical ectopias, and females from the two paternal groups reacted differently to the presence or absence of ectopias. Since females do not have a Y-chromosome, these effects must be through non-genetic mechanisms. Prenatal factors that could have played a role include possible differences in gonadal growth and the presence of different H-Y antigens. Postnatally, the sires and male siblings of the two strains may not have behaved the same toward the female offspring and/or the dams, creating differences in behavior.In summary, the behavior of female offspring of two groups of males, genetically the same except for their Y-chromosomes, was examined. Since females do not receive a Y-chromosome from their fathers, in theory their behavior should not differ. Significant differences were found, indicating that the Y-chromosome, through some indirect mechanism, can affect females of the next generation

Evidence that the Y chromosome influences autoimmune disease in male and female mice

Experimental allergic encephalomyelitis (EAE), an autoimmune model of multiple sclerosis, is a complex disease influenced by genetic, intrinsic, and environmental factors. In this study, we questioned whether parent-of-origin effects influence EAE, using reciprocal F(2) intercross progeny generated between EAE-susceptible SJL/J (S) and EAE-resistant B10.S/SgMcdJ (B) mice. EAE susceptibility and severity were found to be different in female BS × BS intercross mice as compared with females from the three other birth crosses (BS × SB, SB × SB, and SB × BS), and in fact, both traits in female mice resembled those of their male siblings. This masculinization is associated with transmission of the SJL/J Y chromosome and an increased male-to-female sex ratio. Related studies using progeny of C57BL/6J Y-chromosome substitution strains demonstrate that the Y chromosome again influences EAE in both male and female mice, and that the disease course in females resembles that of their male littermates. Importantly, these data provide experimental evidence supporting the existence of a Y-chromosome polymorphism capable of modifying autoimmune disease susceptibility in both males and females

Infralimbic and dorsal raphé microinjection of the 5-HT1B receptor agonist CP-93,129: attenuation of aggressive behavior in CFW male mice

RATIONALE: Aggressive behavior and impaired impulse control have been associated with dysregulations in the serotonergic system and with impaired functioning of the prefrontal cortex. 5-HT(1B) receptors have been shown to specifically modulate several types of offensive aggression. OBJECTIVE: To characterize the relative importance of 2 populations of 5-HT(1B) receptors in the dorsal raphé nucleus (DRN) and infralimbic cortex (ILC) in the modulation of aggressive behavior. METHODS: Male CFW mice were conditioned on a fixed-ratio 5 schedule of reinforcement to self-administer a 6% (w/v) alcohol solution. Mice repeatedly engaged in 5 min aggressive confrontations until aggressive behavior stabilized. Next, a cannula was implanted into either the DRN or the ILC. After recovery, mice were tested for aggression after self-administration of either 1.0 g/kg alcohol or water prior to a microinjection of the 5-HT(1B) agonist, CP-93,129 (0–1.0 µg/infusion). RESULTS: In both the DRN and ILC, CP-93,129 reduced aggressive behaviors after both water and alcohol self-administration. Intra-raphé CP-93,129 dose-dependently reduced both aggressive and locomotor behaviors. However, the anti-aggressive effects of intra-cortical CP-93,129 were behaviorally specific. CONCLUSIONS: These findings highlight the importance of the serotonergic system in the modulation of aggression and suggest that the behaviorally specific effects of 5-HT(1B) receptor agonists are regionally selective. 5-HT(1B) receptors in a medial subregion of the prefrontal cortex, the ILC, appear to be critically involved in the attenuation of species-typical levels of aggression

Abnormalities of Neurotransmission in Drug Addiction

Substance use disorders are prevalent and severe conditions associated with numerous health, social, and economic harms. While the neurobiological mechanisms are still not fully understood, adaptations in multiple neurotransmitter systems have been implicated in the development and maintenance of substance use disorders. The advent of molecular imaging techniques has provided a unique opportunity to better understand abnormalities of neurotransmission in humans with substance use disorders, and this insight may ultimately lead to improved treatment options in the future. This chapter provides a summary of positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies in humans with alcohol, tobacco, cannabis, opioid, and stimulant use disorders. Studies to date provide consistent evidence that the dopaminergic system is disrupted in populations with substance use disorders, although there has been little research in other neurotransmitter systems and findings of existing studies have been mixed. Many PET and SPECT studies investigating abnormalities of neurotransmission in substance use disorder are limited by small sample sizes and over-reliance on male samples without comorbid conditions. In addition, the use of cross-sectional study designs does not make it possible to draw conclusions about causality