Stress-induced hyperthermia in the 5-HT(1A) receptor knockout mouse is normal

Area of Science:

• Neuroscience
• Pharmacology
• Genetics

Background:

• Serotonin 1A (5-HT(1A)) receptor knockout mice often display heightened anxiety.
• The stress-induced hyperthermia (SIH) paradigm assesses anxiolytic drug efficacy.
• Previous research suggests 5-HT(1A) receptor knockout mice may exhibit altered responses in anxiety models.

Purpose of the Study:

• To investigate the phenotype of 5-HT(1A) receptor knockout mice in the SIH paradigm.
• To determine the functional role of the 5-HT(1A) receptor in mediating the effects of the agonist flesinoxan.
• To assess the integrity of the GABA(A)-benzodiazepine receptor complex in knockout mice.

Main Methods:

• Male 129/Sv 5-HT(1A) receptor knockout and wild type mice were subjected to the SIH paradigm.
• Pharmacological challenges included the 5-HT(1A) receptor agonist flesinoxan, antagonist WAY-100635, and GABA(A)-benzodiazepine agonist diazepam.
• Plasma corticosterone levels were measured to assess stress response.

Main Results:

• Flesinoxan elevated corticosterone and decreased SIH in wild type mice, but not in knockout mice.
• The effects of flesinoxan in wild type mice were blocked by WAY-100635.
• Diazepam reduced SIH in both wild type and knockout mice, indicating normal GABA(A)-benzodiazepine receptor function.
• No baseline differences in SIH were observed between genotypes.

Conclusions:

• 5-HT(1A) receptor knockout mice show a normal SIH response.
• The study confirms the critical role of the 5-HT(1A) receptor in mediating flesinoxan's anxiolytic-like effects.
• Results suggest the GABA(A)-benzodiazepine receptor complex functions normally in these knockout mice.