Sex-dependent cognitive phenotype of mice lacking mGluR8.
Metabotropic glutamate receptors (mGluRs) modulate glutamatergic and GABAergic neurotransmission. mGluR8 is generally located presynaptically where it regulates neurotransmitter release. Previously we reported that 6-month-old mGluR8(-/-) male mice show higher measures of anxiety in anxiety tests involving avoidable anxiety-provoking stimuli than age-matched wild-type male mice. In wild-type mice, middle-aged females and males show higher measures of anxiety in such tests and reduced spatial learning than young adults. In this study we evaluated in middle-aged mice the effects of mGluR8 deficiency on measures of anxiety involving avoidable and unavoidable anxiety-provoking stimuli and on cognitive performance and whether these effects are sex-dependent. Female and male mGluR8(-/-) mice showed increased measures of anxiety in the open field. In contrast, male mGluR8(-/-) mice showed increased but female mGluR8(-/-) mice decreased measures of anxiety in the elevated plus maze and the acoustic startle response. mGluR8 deficiency impaired novel location recognition and spatial memory retention in the water maze. The impairment in spatial memory retention in the water maze, but not in novel location recognition, was more pronounced in female than male mice. Thus, potential sex differences in the therapeutic effects of mGluR8 modulation to reduce measures of anxiety and improve cognitive performance should be carefully considered.
Duvoisin
Robert M
RM
Department of Physiology and Pharmacology, Oregon Health & Science University, USA.
Villasana
Laura
L
Pfankuch
Timothy
T
Raber
Jacob
J
D000161:Acoustic Stimulation / Q000379:methods; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000235:genetics; D003071:Cognition / Q000502:physiology*; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D010641:Phenotype; D018094:Receptors, Metabotropic Glutamate / Q000172:deficiency*; D021641:Recognition, Psychology / Q000502:physiology; D013216:Reflex, Startle / Q000235:genetics; D012727:Sex Characteristics
D018094:Receptors, Metabotropic Glutamate; C111435:metabotropic glutamate receptor 8