Myron Hofer | PubMed Health

PubMed2007

Developing a framework for development: a discussion.

A multitude of scientific disciplines study the development of behavior. Their use of different methodological and conceptual approaches makes integration of findings difficult. In a symposium at the 38th Annual Meeting of the International Society for Developmental Psychobiology in Washington DC, the question was discussed if a general theory of development could unify the field. The three participants explain their views and discuss the possibility of a theoretical framework for development.

Animals↗

PubMed2003

Maternal effects in infant and adult phenotypes of 5HT1A and 5HT1B receptor knockout mice.

The influence of the pre- and postweaning maternal environment on the offspring's phenotype was examined in 5-HT1A and 5-HT1B receptor knockout mice (KO1A and KO1B, respectively). We have previously shown that, when born to and raised by homozygous dams of the same genotype, adult KO1A are more anxious than wild-type (WT) mice, and adult KO1B are hyperactive and slightly less anxious than WT mice. We extend our studies here to the behavioral results of the offspring's own genotype, when the dam's genotype is constant, and the effects of the dam's genotype when the offspring's genotype is constant. In Experiments 1 and 2, KO1A-/- pups produced less ultrasonic vocalizations (USV) than controls in an isolation test on postnatal Day 7 when born to and reared by KO1A dams, either -/- or +/-. Heterozygous F1 pups reared by KO1A-/- dams produced more USV and were less anxious in the plus-maze at 2 to 3 months of age than F1 pups born to and reared by WT dams (Experiment 3). F1 pups reared by KO1B-/- dams produced less USV and were more anxious in the plus-maze than F1 pups reared by WT dams (Experiment 4). The results support a role for maternal effects that may comprise direct effects such as the dam's behavior and nutritional care of the pup, and possibly more complex indirect effects through the establishment of idiosyncratic dam-pup dyadic interactions. We recommend that breeding techniques that rely on same genotype (mutant-mutant or WT-WT) breeding pairs not be used to generate offspring when the focus of research is the study of gene function, but rather when familial effects need to be studied.

Animals↗

PubMedDate not supplied

Juvenile 5HT(1B) receptor knockout mice exhibit reduced pharmacological sensitivity to 5HT(1A) receptor activation.

Serotonin is an important modulator of anxiety and thus drugs that act on this system have frequently been shown to be either anxiogenic or anxiolytic. In addition serotonin has important trophic functions during early development and disruption of serotonin homeostasis is likely to have long-lasting repercussions in the adult. In the present study we examined the contribution of two serotonin receptor subtypes (5HT(1A) and 5HT(1B)) to the pathophysiology of anxiety during development. For this, we have studied homozygous knockout mice lacking the 5HT(1B) receptor and examined the effect of pharmacological manipulations of 5HT(1A) and 5HT(1B) receptors on locomotor activity and emission of ultrasonic vocalization (USV) in 7-8 days old mice. As shown before, drug naïve 5HT(1B) knockout pups showed reduced USV and were hyperactive, in comparison to wild type controls. The administration of RU24969 (a 5HT(1A/1B) agonist) showed a dose-dependent decrease in USV in the wild type and a biphasic effect in the mutants and resulted in dose-dependent increase in activity in the wild type and, to a lesser extent, in the knockouts. The selective 5HT(1A) agonist, 8OH-DPAT, dose-dependently blocked vocalization in both genotypes and also increased locomotion. To differentially activate 5HT(1B) receptors we first blocked 5HT(1A) receptors with WAY100315 and then treated with RU24969. At a high testing temperature, pretreatment with WAY100315 resulted in an anxiogenic effect in wild type pups but not in the knockouts. In agreement with our findings that 5HT(1B) knockout mice were in general less sensitive to 5HT(1A) activation, 5HT(1A) receptor binding was reduced in the knockouts in comparison to controls. Finally, treatment with diazepam dose-dependently decreased USVs in both group with the knockouts showing enhanced sensitivity to this drug. Our results show that important adaptations to a disturbance of serotonin homeostasis occur during the first week of life within the serotonergic system. The observed decreased in sensitivity of 5HT(1B) knockout mice to 5HT(1A) and increased to GABA(A) manipulations are discussed within the context of serotonergic plasticity during development and the implication for clinical treatment of anxiety in genetically predisposed individuals.

Animals↗