Acute stress or systemic insulin injection increases flunitrazepam sensitive-GABA_A receptor density in synaptosomes of chick forebrain: Modulation by systemic epinephrine

Abstract

Interactions between acute stress and systemic insulin and epinephrine on GABA_A receptor density in the forebrain were studied. Here, 10 day-old chicks were intraperitoneally injected with insulin, epinephrine or vehicle and then immediately stressed by partial water immersion for 15 min and killed by decapitation. Non-stressed controls were similarly injected, then returned to their rearing boxes for 15 min and then killed. Forebrains were dissected and GABA_A receptor density was measured ex vivo in synaptosomes by ³[H]-flunitrazepam binding assay. In non-stressed chicks, insulin at 1.25, 2.50 and 5.00 IU/kg of body weight (non-hypoglycemic doses) increased B_max by 33, 53 and 44% compared to saline, respectively. A similar increase of 41% was observed in receptor density after stress. However, the insulin effect was not additive to the stress-induced increase suggesting that both effects occur through similar mechanisms. In contrast, epinephrine, at 0.25 and 0.5 mg/kg did not induce any changes in B_max in non-stressed chicks. Nevertheless, after stress these doses increased the receptor density by about 13 and 27%, respectively. Similarly, the same epinephrine doses co-administered with insulin (2.50 IU/kg), increased the receptor density by about 20% compared to insulin alone. These results suggest that systemic epinephrine, perhaps by evoking central norepinephrine release, modulates the increase in forebrain GABA_A receptor binding induced by both insulin and stress.

• Acute stress
• epinephrine
• GABA_A R density
• Gallus gallus domesticus
• insulin
• water immersion stress