Reduction in 5-HT1A receptor density, 5-HT1A mRNA expression, and functional correlates for 5-HT1A receptors in genetically defined aggressive rats

Abstract

The present experiments tested the hypothesis that one of the critical mechanisms underlying genetically defined aggressiveness involves brain serotonin 5-HT1A receptors. 5-HT1A receptor density, the receptor mRNA expression in brain structures, and functional correlates for 5-HT1A receptors identified as 8-OH-DPAT-induced hypothermia and lower lip retraction (LLR) were studied in Norway rats bred for 59 generations for the lack of aggressiveness and for high affective aggressiveness with respect to man. Considerable differences between the highly aggressive and the nonaggressive rats were shown in all three traits. A significant decrease in B(max) of specific receptor binding of [3H]8-OH-DPAT in the frontal cortex, hypothalamus, and amygdala and a reduction in 5-HT1A receptor mRNA expression in the midbrain of aggressive rats were found. 5-HT1A receptor agonist 8-OH-DPAT (0.5 mg/kg, i.p.) produced a distinct hypothermic reaction in nonaggressive rats and did not affect significantly the body temperature in aggressive rats. Similar differences were revealed in 8-OH-DPAT-induced LLR: LLR was expressed much more in nonaggressive than in aggressive animals. Additionally, 8-OH-DPAT (0.5 mg/kg i.p.) treatment significantly attenuated the aggressive response to man. The results demonstrated an association of aggressiveness with reduced 5-HT1A receptor expression and function, thereby providing support for the view favoring the idea that brain HT1A receptor contributes to the genetically defined individual differences in aggressiveness.

Genetic Architecture of Tameness in a Rat Model of Animal Domestication

“…Overlap of QTL for tameness-associated traits: Previous studies have identified a multitude of phenotypic differences between the tame and the aggressive lines of rats (Naumenko et al 1989;Plyusnina and Oskina 1997;Popova et al 2005;. However, the behavioral response to humans was the only criterion used during selection.…”

“…Correlations between phenotypes: Earlier work revealed a multitude of phenotypic differences between the tame and the aggressive rats, including behavioral, anatomical, hormonal, and neurochemical differences (Naumenko et al 1989;Plyusnina and Oskina 1997;Popova et al 2005;. If these differences are caused by the same genetic loci, they should be correlated in the F 2 animals.…”

Effects of Activation and Blockade of Serotonin 5-HT1A Receptors on the Immune Response in Rats Selected for Different Levels of Aggressiveness

“…The results of previous studies have indicated significant differences in the functional state and expression of 5-HT 1A receptors between highly aggressive and nonaggressive rats [23] [25] [35]. For example, rats of the aggressive line showed a reduced functional activity of the brain 5-HT 1A receptors and lower expression of the 5-HT 1A receptor gene in the midbrain [23] [25] [35].…”

“…For example, rats of the aggressive line showed a reduced functional activity of the brain 5-HT 1A receptors and lower expression of the 5-HT 1A receptor gene in the midbrain [23] [25] [35].…”

“…Compared to nonaggressive line, highly aggressive rats showed an increased humoral immune response to sheep red blood cells (SRBC). There are also data that these rat lines differ in the activity of the 5-HTergic system and 5-HT 1A receptors [23] [25] [33]- [38].…”