The 5-HT(1A) receptor knockout mouse and anxiety.
The 5-HT(1A) receptor has been implicated in the modulation of anxiety processes, mainly via pharmacological experiments. The recent production, in three independent research groups, of 5-HT(1A) receptor knockout (R KO) mice in three different genetic backgrounds (C57BL/6J, 129/Sv, Swiss-Webster) led to the intriguing finding that all mice, independent from the genetic background strain from which the null mutants were made, showed an "anxious" phenotype compared to corresponding wild-type mice. The present paper reviews the behavioral findings in these three KO lines and focuses on new findings in the 129/Sv-KO mice. These mice were more anxious or stress-prone only under specific conditions (high stress) and not as broadly as suggested from the initial studies. The 5-HT(1A) R KO made in the Swiss-Webster background displays disturbances in the GABA(A)-benzodiazepine (BZ) receptor system in the brain, including downregulation of GABA(A) alpha1 and alpha2 subunits in the amygdala. In contrast, the GABA(A)-BZ receptor system seems to function normally in the 5-HT(1A) R KO in the 129/Sv background suggesting that changes in the GABA(A)-BZ receptor system may not be a prerequisite for anxiety but rather could have a modifying effect on this phenotype. It can be concluded that the constitutive absence of the 5-HT(1A) receptor gene and receptor leads to a more "anxious" mouse, dependent on the stress level but independent from the strain. Depending on the genetic background, this null mutation may be associated with changes in GABA(A)-ergic neurotransmission. It is as yet unclear which mechanisms are involved in this intriguing differentiation.
Olivier
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B
Department of Psychopharmacology, Faculty of Pharmacy, Utrecht University, Sorbonnelaan 16, 3584CA Utrecht, The Netherlands. b.olivier@pharm.uu.nl
Pattij
T
T
Wood
S J
SJ
Oosting
R
R
Sarnyai
Z
Z
Toth
M
M
D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000503:physiopathology; D001143:Arousal / Q000235:genetics* / Q000502:physiology; D005838:Genotype; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009415:Nerve Net / Q000503:physiopathology; D011985:Receptors, Serotonin / Q000235:genetics*; D044263:Receptors, Serotonin, 5-HT1; D012931:Social Environment
D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1