Deficient NRG1-ERBB signaling alters social approach: relevance to genetic mouse models of schizophrenia

Growth factor Neuregulin 1 (NRG1) plays an essential role in development and organization of the cerebral cortex. NRG1 and its receptors, ERBB3 and ERBB4, have been implicated in genetic susceptibility for schizophrenia. Disease symptoms include asociality and altered social interaction. To investigate the role of NRG1-ERBB signaling in social behavior, mice heterozygous for an Nrg1 null allele (Nrg1+/−), and mice with conditional ablation of Erbb3 or Erbb4 in the central nervous system, were evaluated for sociability and social novelty preference in a three-chambered choice task. Results showed that deficiencies in NRG1 or ERBB3 significantly enhanced sociability. All of the mutant groups demonstrated a lack of social novelty preference, in contrast to their respective wild-type controls. Effects of NRG1, ERBB3, or ERBB4 deficiency on social behavior could not be attributed to general changes in anxiety-like behavior, activity, or loss of olfactory ability. Nrg1+/− pups did not exhibit changes in isolation-induced ultrasonic vocalizations, a measure of emotional reactivity. Overall, these findings provide evidence that social behavior is mediated by NRG1-ERBB signaling

Ontogeny of PFC-related behaviours is sensitive to a single non-invasive dose of methamphetamine in neonatal gerbils (Meriones unguiculatus).

Dawirs RR, Teuchert-Noodt G, Czaniera R. Ontogeny of PFC-related behaviours is sensitive to a single non-invasive dose of methamphetamine in neonatal gerbils (Meriones unguiculatus). J Neural Transm. 1996;103(11):1235-1245.A single dose of methamphetamine (50 mg/kg; i.p.) was administered to neonatal male gerbils (Meriones unguiculatus) aged 14 days, and adult prefrontal cortex (PFC)-related behaviours were analysed and compared with saline-treated controls at the age of postnatal day 90. For that purpose, animals were tested for open-field activities and y-maze delayed alternation. This solitary and non-invasive drug challenge, which has recently been found to initiate serious restraint in maturation of the mesoprefrontal dopamine (DA)-system (Dawirs et al., 1994), induces a significant delayed alternation impairment as well as significant increases in open-field motor activity and emotionality. Since an undisturbed development of the prefrontal DA-innervation seems to be a precondition for the maturation of normal PFC-related behaviours, a single early methamphetamine impact may be a suitable animal model for further investigation of structural and functional aspects of non-invasively induced behavioural deficits in rodents. The present results are discussed with regard to the assumption that hypofunctional mesoprefrontal DA-systems might be basic to schizophrenic behaviours in man