5 research outputs found
Polymorphism in the Tyrosine Hydroxylase (TH) Gene Is Associated with Activity-Impulsivity in German Shepherd Dogs
We investigated the association between repeat polymorphism in intron 4 of the tyrosine hydroxylase (TH) gene and two personality traits, activity-impulsivity and inattention, in German Shepherd Dogs. The behaviour of 104 dogs was characterized by two instruments: (1) the previously validated Dog-Attention Deficit Hyperactivity Disorder Rating Scale (Dog-ADHD RS) filled in by the dog owners and (2) the newly developed Activity-impulsivity Behavioural Scale (AIBS) containing four subtests, scored by the experimenters. Internal consistency, inter-observer reliability, test-retest reliability and convergent validity were demonstrated for AIBS
The absence of P2X7 receptors (P2rx7) on non-haematopoietic cells leads to selective alteration in mood-related behaviour with dysregulated gene expression and stress reactivity in mice
The purpose of this study was to explore how genetic deletion
and pharmacological antagonism of the P2X7 receptor (P2rx7)
alter mood-related behaviour, gene expression and stress
reactivity in the brain. The forced swim test (FST), tail
suspension test (TST) and amphetamine-induced hyperlocomotion
(AH) tests were used in wild-type (P2rx7+/+) and P2rx7-deficient
(P2rx7-/-) mice. Biogenic amine levels were analysed in the
amygdala and striatum, adrenocorticotropic hormone (ACTH) and
corticosterone levels were measured in the plasma and pituitary
after restraint stress. Chimeric mice were generated by bone
marrow transplantation. A whole genome microarray analysis with
real-time polymerase chain reaction validation was performed on
the amygdala. In the absence of P2rx7s decreased behavioural
despair in the FST, reduced immobility in the TST and attenuated
amphetamine-induced hyperactivity were detected. Basal
norepinephrine levels were elevated in the amygdala, whereas
stress-induced ACTH and corticosterone responses were alleviated
in P2rx7-/- mice. Sub-acute treatment with the selective P2rx7
antagonist, Brilliant Blue G, reproduced the effect of genetic
deletion in the TST and AH test in P2rx7+/+ but not P2rx7-/-
mice. No change in behavioural phenotype was observed in
chimeras lacking the P2rx7 in their haematopoietic compartment.
Whole genome microarray analysis indicated a widespread up- and
down-regulation of genes crucial for synaptic function and
neuroplasticity by genetic deletion. Here, we present evidence
that the absence of P2rx7s on non-haematopoietic cells leads to
a mood-stabilizing phenotype in several behavioural models and
suggest a therapeutic potential of P2rx7 antagonists for the
treatment of mood disorders
Association between tyrosine hydroxylase intron 4 genotypes and activity-impulsivity related phenotypes.
<p>(A) Dog-ADHD RS activity-impulsivity scale; (B) Activity-Impulsivity Behavioural Scale (AIBS). 1/2 genotype represents the group of individuals possessing at least one short allele. Subjects in the 2/2 genotype possess two long alleles. Box-plot figures with sample minimum and maximum, lower and upper quartiles and medians. * indicates significant differences (* p<0.05; ** p<0.01).</p
Mean scores of the AIBS behavioural variables.
<p>Mean scores of the AIBS behavioural variables.</p