A polymorphism in this gene has been associated with opioid effects on analgesia and methadone replacement dose (Lotsch et al. 2010). A study examining dopamine-dependent phenotypes in GIRK2 knockout mice noted the presence of dopamine-dependent hyperactivity and enhanced responses to drugs that stimulate dopamine neurotransmission (Arora et al. 2010). However, these phenotypes were not solely attributable to the loss of GIRK (1/2) signaling in dopamine neurons, but could be due to adaptations in the mesolimbic dopamine system that facilitated excitatory glutamatergic neurotransmission. Therefore the authors suggest that drugs of abuse may evoke adaptations to promote chronic use through a regulation of GIRK signaling strength in dopaminergic neurons or their input neurons.
