Genetic determinants of sensitivity to pentobarbital in inbred mice

Abstract

Overall, these results suggest that there are multiple genetic determinants of behavioral sensitivity to PB effects. That is, genetically influenced sensitivity to PB is not monolithic, but is somewhat specific to the particular response variable studied, a result that also characterizes genetic control of responses to other drugs.

Differential sensitivity to the motor and hypothermic effects of the GABAB receptor agonist baclofen in various mouse strains

“…Further, this response may be absent altogether, as we observed in the C3H/HeOuJIco strain (Table 2,Figs.1f,4a). Variations in the body temperature response profiles of different mouse strains have also been previously reported for pentobarbital (Crabbe et al 2002), ethanol (Crabbe et al 1994), diazepam and morphine ). Although it is not necessarily expected that different drugs will give similar hypothermic responses in different strains, it is interesting to note that in our studies the C3H/HeOuJIco strain body temperature was unaffected by baclofen, and in the study of Belknap et al (1998) the C3H/HeJ strain did not show any hypothermia to morphine.…”

“…Although it is not necessarily expected that different drugs will give similar hypothermic responses in different strains, it is interesting to note that in our studies the C3H/HeOuJIco strain body temperature was unaffected by baclofen, and in the study of Belknap et al (1998) the C3H/HeJ strain did not show any hypothermia to morphine. Conversely, the 129/SvPasIco strain in this study responded with a high degree of both ataxia and hypothermia to baclofen, and the 129P3/J (formerly 129/J; Festing et al 1999) strain was shown to be highly susceptible to the hypothermic and ataxic effects of pentobarbitone in comparison with other strains (Crabbe et al 2002). However, it should be noted that extensive genetic variability between the 129 substrains exist (Simpson et al 1997;Threadgill et al 1997), which makes drawing comparisons about like-phenotypes within this strain more complicated.…”

“…This method has been previously reported to estimate the degree of shared genetic control between traits (Hegmann and Possidente 1981;Crabbe et al 2002).…”

“…Despite this, to our knowledge, there is no data investigating whether these responses are under the same genetic control. Indeed recent strain comparisons in mice suggest that individual behavioural responses to GABA A receptor ligands (ethanol, diazepam and pentobarbital), including motor in-coordination and hypothermia, have differential genetic determinants (Crabbe et al , 1994(Crabbe et al , 2002.…”

Genetic Approaches to Modeling Anxiety in Animals

“…Certainly, many studies have demonstrated phenotypic differences in anxiety-related behaviors and stress responsiveness between inbred strains; for example, the highly anxious and stress-sensitive phenotype of BALB/c mice, has lead some researchers to propose this strain as a suitable model for pathological anxiety per se (Anisman and Zacharko 1992;Griebel et al 2000;Anisman et al 2001;Belzung 2001). Inbred strains also show differences in their responses to a number of pharmacological agents, suggesting that genetic-based neurobiological differences underlie the observer behavioral variations (reviewed in Crawley et al 1997;Crawley 2007), and for examples, see (Belknap et al 1989;Crabbe et al 1994;Crabbe et al 1998;Griebel et al 2000;Lucki et al 2001;Crabbe et al 2002;Jacobson and Cryan 2005). As such, the inbred mouse has been recognized as an immensely valuable tool for fundamental genetic research and genetic modeling of human disease states.…”