High-affinity choline transport regulation by drug administration during postnatal development

Area of Science:

• Neuroscience
• Pharmacology
• Developmental Biology

Background:

• High-affinity choline transport sites bind [3H]hemicholinium-3.
• These sites are regulated by in vivo drug treatments, mirroring effects on acetylcholine release and choline transport.

Purpose of the Study:

• To investigate the developmental regulation of hemicholinium-3 binding sites in rat striatum and cortex.
• To examine how in vivo drug administration affects these binding sites at different developmental stages (postnatal days 5, 15, and adult).

Main Methods:

• Administration of drugs (nicotine, haloperidol, oxotremorine, pentobarbital, atropine, apomorphine) or saline intraperitoneally to rats of different ages.
• Assay of striatal and cortical membrane preparations for [3H]hemicholinium-3 binding.
• Comparison of binding levels across developmental stages and drug treatment groups.

Main Results:

• Control [3H]hemicholinium-3 binding increased significantly in striatum (days 5-15) and in both striatum and cortex (after day 15).
• Nicotine increased binding at all ages, with greater effects at day 5. Haloperidol increased binding in striatum, with larger effects at day 5.
• Oxotremorine reduced binding without developmental change, while pentobarbital reduced striatal binding with no developmental change. Atropine and apomorphine had no effect.

Conclusions:

• Drug treatments effective in adult rats were effective by postnatal day 5, suggesting early development of regulatory mechanisms.
• Cholinergic terminals in early development are regulated by similar nicotinic, muscarinic, dopaminergic, and sedative-hypnotic mechanisms as in adults.
• Observed changes in drug effect magnitude may be due to developmental differences in drug metabolism or regulation.