α5 nAChR

2022-05-26: reference:

α5 nAChR #

• Deletion of α5 nicotine receptor subunits abolishes nicotinic aversive motivational effects in a manner that phenocopies dopamine receptor antagonism
  • Knockout mice exhibit: increased nicotine intake & reduced sensitiviy to its behavioral effects, and show increased attentional performance(?)
    • Less prone to desensitization.
• The α5 Subunit Regulates the Expression and Function of α4*-Containing Neuronal Nicotinic Acetylcholine Receptors in the Ventral-Tegmental Area
  • While the presence of the α5 subunit blunts the desensitization of nAChRs following nicotine exposure, it does not alter the amount of ethanol potentiation of VTA dopaminergic neurons.
• Nicotinic α5 subunits drive developmental changes in the activation and morphology of prefrontal cortex layer VI neurons
• Does not form homomers, needing at least another α subunit, as well as a β2 or β4.
• Nearly all α5-containing receptors are located on dopamine axon terminals (i.e. of the Striatum I think): Identification of the nicotinic receptor subtypes expressed on dopaminergic terminals in the rat striatum (Zoli 2002)
• The Nicotinic Acetylcholine Receptor α5 Subunit Plays a Key Role in Attention Circuitry and Accuracy
  • the relatively rare α5 subunit of the nicotinic acetylcholine receptor powerfully enhances nicotinic currents in layer VI pyramidal neurons in prefrontal cortical brain slices from adult mice
• Nicotinic α5 receptor subunit mRNA expression is associated with distant 5’ upstream polymorphisms This SNP cluster, in complete linkage disequilibrium (LD), fully account for a >2.5-fold allelic expression difference and a fourfold increase in overall CHRNA5 mRNA expression.
  • rs1979905 (Me: CC)
  • rs1979906 (Me: TT)
  • rs1979907 (Me: –)
  • rs880395 (Me: GG)
  • rs905740 (Me: CC) = ++
  • rs7164030 (Me: –)