Early-life propofol exposure does not affect later-life GABAergic inhibition, seizure induction, or social behavior

Abstract

The early developing brain is especially vulnerable to anesthesia, which can result in long lasting functional changes. We examined the effects of early-life propofol on adult excitatory-inhibitory balance and behavior. Postnatal day 7 male mice were exposed to propofol (250 mg/kg i.p.) and anesthesia was maintained for 2 h; control mice were given the same volume of isotonic saline and treated identically. The behavior and electrophysiology experiments were conducted when the mice were adults. We found that a 2-h neonatal propofol exposure did not significantly reduce paired pulse inhibition, alter the effect of muscimol (3 µM) to inhibit field excitatory postsynaptic potentials or alter the effect of bicuculline (100 µM) to increase the population spike in the CA1 region of hippocampal slices from adult mice. Neonatal propofol did not alter the evoked seizure response to pentylenetetrazol in adult mice. Neonatal propofol did not affect anxiety, as measured in the open field apparatus, depression-like behavior, as measured by the forced swim test, or social interactions with novel mice, in either the three-chamber or reciprocal social tests. These results were different from those with neonatal sevoflurane which demonstrated reduced adult GABAergic inhibition, increased seizure susceptibility and reduced social interaction. Even though sevoflurane and propofol both prominently enhance GABA inhibition, they have unique properties that alter the long-term effects of early-life exposure. These results indicate that clinical studies grouping several general anesthetic agents in a single group should be interpreted with great caution when examining long-term effects.

Keywords

• Propofol
• Early-life anesthesia
• Brain development
• GABAergic inhibition
• Social behavior
• Cognitive function