Reduction in striatal D2 dopamine receptor mRNA and binding following AF64A lesions

Mol Chem Neuropathol. 1993 Sep;20(1):81-96. doi: 10.1007/BF03160071.

Abstract

Unilateral lesions by a cholinotoxin, receptor autoradiography, and in situ hybridization techniques were employed to determine if dopaminergic receptors are located on cholinergic interneurons in the caudate-putamen (CPu). Lesion of the CPu with small amounts of the cholinotoxin AF64A resulted in a significant decrease in D2 receptor mRNA and D2 receptor binding. The loss was more pronounced in lateral and central portions of the CPu. Results obtained using [3H] SCH23390 binding to D1 receptors indicated that there was no change in this dopamine receptor subtype in the AF64A-lesioned CPu. A decrease in D2 receptor mRNA and receptor binding in AF64A-lesioned animals indicates that a population of postsynaptic D2 receptors is associated with the cholinergic interneurons. Lack of any change in [3H]SCH23390 binding in the AF64A-lesioned animals suggests that D1 receptors are not located on cholinergic neurons. These results provide evidence to support the selectivity of the lesion when used as indicated.

MeSH terms

  • Animals
  • Autoradiography
  • Aziridines / toxicity*
  • Base Sequence
  • Benzazepines / pharmacology
  • Caudate Nucleus / drug effects
  • Caudate Nucleus / metabolism*
  • Choline / analogs & derivatives*
  • Choline / toxicity
  • In Situ Hybridization
  • Molecular Sequence Data
  • Neuromuscular Blocking Agents / toxicity*
  • Neurons / drug effects
  • Neurons / metabolism
  • Putamen / drug effects
  • Putamen / metabolism*
  • RNA, Messenger / biosynthesis*
  • Rats
  • Receptors, Dopamine D1 / drug effects
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / biosynthesis*
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D2 / metabolism

Substances

  • Aziridines
  • Benzazepines
  • Neuromuscular Blocking Agents
  • RNA, Messenger
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • ethylcholine aziridinium
  • Choline