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At least 1,279 records · Page 71Linked to original sources
PubMed1998

Behavior in mice with targeted disruption of single genes.

The use of mice with targeted deletion, or knockout, of specific genes provides a relatively new approach to establish the molecular bases of behavior. As with all ablation studies, the interpretation of behavioral data may be limited by the technique. For example, indirect effects of the missing gene may affect behavior, rather than the missing gene per se. Also, because the missing gene might affect many developmental processes throughout ontogeny and because up-regulation or compensatory mechanisms may be activated in knockouts, behavioral data from mice with targeted gene deletions should be interpreted with caution. The development of conditional knockouts, in which a specific gene can be inactivated any time during ontogeny, should allow investigators to avoid these conceptual shortcomings associated with behavioral data from knockouts in the near future. The behavioral alterations reported in knockout mice are reviewed here. Many dramatic changes in complex motivated behaviors including aggression, sexual, ingestive, and parental behaviors, have been reported for knockouts. There have also been many reports of alterations in sensorimotor abilities and spontaneous activity, as well as impairments in balance, coordination, and gait. Impaired learning and memory have also been reported for mice with targeted disruption of specific genes. Taken together, the use of knockouts will provide an important new tool to understand the mechanisms underlying behavior.

Animals↗
PubMed1998

New functions for nicotinic acetylcholine receptors?

Although the neuronal nicotinic acetylcholine receptor is found in most parts of the brain, not much is known about its functional significance. At least ten different subunits are expressed in the central nervous system, theoretically able to give rise to more than a thousand different receptor subtypes. Despite, or perhaps because of, this astonishing diversity, the biological role of this receptor type remains to be investigated. It has recently been found that a mutated alpha4-subunit is associated with an inherited epilepsy syndrome. A missense mutation replacing a serine in position 248 of the second transmembrane domain by phenylalanine leads to hypoactivity of the receptor due to accelerated desensitization and delayed resensitization. Thus, for the first time a link between a human disease and a mutated neuronal nicotinic acetylcholine receptor has been found, pointing to a possible involvement of this ligand-gated receptor family in the modulation of brain excitability levels.

Animals↗
PubMed1999

Use of SHIRPA and discriminant analysis to characterise marked differences in the behavioural phenotype of six inbred mouse strains.

Detailed characterisation of six inbred strains of mice commonly used in transgenic and knockout research was carried out using a battery of behavioural tests (SHIRPA) followed by discriminant analysis of the data. In the primary observation screen, DBA/2 mice were relatively irritable and vocalised during handling. C57BL/6 were hyperactive as measured by transfer arousal, arena activity and touch-escape tests. By contrast, C3H were markedly hypoactive, had significantly enhanced grip strength and were also significantly impaired on the visual placing task. In the elevated plus-maze, BALB/c mice showed the highest level of open arm entries and time spent in the open arms, indicating the lowest level of anxiety. There was a clear dissociation of strains on exploratory activity, as measured in the holeboard test and spontaneous locomotor activity (LMA). DBA/2 mice were hyperactive in LMA but demonstrated relatively low levels of holeboard exploration. None of the six strains learnt the water maze spatial learning task particularly well. C57BL/6 and 129/Sv demonstrated most ability and C3H showed no evidence of having acquired the task. The SHIRPA screening battery and discriminant analysis of the data have enabled us to determine the relevant contribution of a number of behavioural measurements to the marked differences in phenotype of mouse strains. These data confirm the importance of carrying out a comprehensive profile in order to accurately characterise the phenotype of gene-targeted and transgenic mice.

Animals↗
PubMed1984

Within-pair differences in newborn twins: effects of gender and gestational age on behavior.

The behavior of 120 full term and 160 preterm newborn twins was assessed in several key areas: Irritability, soothability, reactivity, reinforcement value, and activity level. Infants were assessed during various situations so that aggregate, or summary, scores representing each behavioral area could be obtained. Evaluations were made during a feeding period, an active sleep period, an awake alert period during which orienting and interactional behaviors were observed, a quiet period during which reactivity to stress was observed, and any fussy periods during which irritability and soothability were assessed. Significant within-twin-pair concordance of behavior was obtained for each of the areas of behavior, suggesting the influence of constitutional variables on neonatal behavior. Analysis of these data by sex resulted in significant within-pair concordance of behavior for same-sex but not for opposite-sex twins. The actual ratings on these behaviors differentiated between full term and preterm infants. Increased behavioral deviance was observed with increasing prematurity in the areas of soothability and activity level. The results are discussed in terms of increased risk factors for preterm twins.

Child Behavior↗
PubMed1988

Aristotle's biopolitics: a defense of biological teleology against biological nihilism.

Modern Darwinian biology seems to promote nihilism, for it seems to teach that there is no rationally discoverable standard in nature for giving meaning to life. The purpose of this article is to argue for a revival of Aristotle's biological teleology as a reasonable alternative to biological nihilism. The article begins with Edward Wilson's vain struggle against nihilism. Then it is argued that a teleological understanding of nature is assumed in the practice of medicine, as illustrated by one case from Oliver Sacks' neurological practice. The article then considers the importance of biological teleology for Aristotle's moral and political philosophy, and attention is given to some points of agreement and disagreement with contemporary sociobiologists. The main part of the article is then devoted to a defense of Aristotle's biology against the five objections that might be made by a Darwinian biologist. Finally, the article illustrates the practical implications of this issue for bioethics by considering the recent work of Engelhardt.

Animals↗
PubMed2002

The Maudsley Reactive and Nonreactive strains: a new perspective.

Research on the Maudsley Reactive and Maudsley Nonreactive strains conducted primarily between 1980 and 2001 is reviewed. One line of research, which has found consistent differences between the Harrington derivation of the Maudsley Reactive (MR/Har) and Maudsley Nonreactive (MNRA/Har) strains in conflict situations, appears to support the traditional view of the two strains as representing models of global differences in emotionality. In contrast, comparisons of the two strains in two commonly used tests that involve a component of fear either do not reveal differences between the strains (escape-avoidance conditioning) or are inconsistent in expression (elevated plus maze). Emphasis is placed on the importance of recognizing that most of the phenotypic differences discovered among selected inbred strains, including the Maudsleys, will inevitably be unrelated to the original selection criterion, but that many of these phenotypic differences will have their own intrinsic interest. For example, the fact that, relative to MNRA/Har, two bottle ethanol preference is greater in MR/Har rats and that MR/Har rats exhibit greater exploration of novel stimuli when these are presented in a familiar environment may have little to do with the hypothesized differences in emotionality among the strains. It is suggested the MR/Har drinking pattern in alcohol preference tests, which is characterized by considerable variability, may complement other models of alcoholism, especially in the investigation of environmental influences which contribute to the variability. In the case of strain differences in response to novelty, this may help explain some of the inconsistencies in findings in the elevated plus maze, which, aside from provoking fear, also contains an important element of novelty. Finally, it has been found that alterations in the peripheral sympathetic nervous system (PSNS) are correlated with strain differences in open-field defecation (OFD) in the Maudsley model, and it has been proposed that the lower OFD of MNRA/Har rats is a direct result of sympathetic inhibition of colonic motility. These strain differences in the PSNS are furthermore associated with important alterations in the response of the central noradrenergic system to acute and chronic stress. It is hypothesized that genes may have influenced PSNS tone by altering CNS structures with descending projections. If the link between low levels of OFD and higher peripheral sympathetic tone is supported by additional experiments, this will force reconsideration of OFD as an index of emotionality.

Alcohol Drinking↗
PubMed1999

A genetic association for cigarette smoking behavior.

Dopaminergic genes are likely candidates for heritable influences on cigarette smoking. In an accompanying article, Lerman et al. (1999) report associations between allele 9 of a dopamine transporter gene polymorphism (SLC6A3-9) and lack of smoking, late initiation of smoking, and length of quitting attempts. The present investigation extended their study by examining both smoking behavior and personality traits in a diverse population of nonsmokers, current smokers, and former smokers (N = 1,107). A significant association between SLC6A3-9 and smoking status was confirmed and was due to an effect on cessation rather than initiation. The SLC6A3-9 polymorphism was also associated with low scores for novelty seeking, which was the most significant personality correlate of smoking cessation. It is hypothesized that individuals carrying the SLC6A3-9 polymorphism have altered dopamine transmission, which reduces their need for novelty and reward by external stimuli, including cigarettes.

Adult↗