Extinction in preweanling rats does not involve NMDA receptors

Area of Science:

• Neuroscience
• Developmental Psychology
• Behavioral Pharmacology

Background:

• N-methyl-d-aspartate receptors (NMDAr) are crucial for fear extinction in adult rats.
• NMDAr antagonists impair extinction retention, while agonists enhance it.
• The role of NMDAr in fear extinction during early development is not well understood.

Purpose of the Study:

• To investigate the effect of the NMDAr antagonist MK-801 on fear extinction in developing rats.
• To determine the developmental trajectory of NMDAr involvement in fear extinction and re-extinction.

Main Methods:

• Rats were conditioned to a conditioned stimulus (CS) paired with an unconditioned stimulus (US) on postnatal day (P)16.
• Extinction or re-extinction sessions were conducted at different ages (P17, P24, P26) with or without MK-801 administration.
• Fear retention was tested drug-free on P25 or P27.

Main Results:

• MK-801 impaired extinction retention when extinction occurred on P24, but not on P17, indicating age-dependent NMDAr involvement.
• Rats extinguished on P24 showed NMDAr-independent re-extinction, while those extinguished on P17 did not.
• These findings suggest a shift from NMDAr-dependent to NMDAr-independent fear extinction during development.

Conclusions:

• Fear extinction is NMDAr-dependent at P24 but NMDAr-independent at P17 in rats.
• A developmental transition in the NMDAr system's role in fear extinction and re-extinction is evident.
• Qualitatively different systems mediate fear extinction early in life compared to adulthood.