in striatum and NAc is also thought to be critical for mediating the association between drugs of abuse and cues in the environment that drive drug craving and relapse to drug use after abstinence (Exley and Cragg, 2008). The effects of striatal ACh are mediated in part through activation of nAChRs on dopaminergic terminals, leading to tonic, low level DA release when cholinergic interneurons are firing. The pause results in decreased tonic DA release but maintained phasic DA release (Exley and Cragg, 2008). In contrast, mAChRs reduce the probability of glutamate release from excitatory afferents to the striatum, negatively regulating the ability of these inputs to drive striatal activity (Barral et al., 1999; Higley et al., 2009; Pakhotin and Bracci, 2007). Reduced concentration of glutamate in the synaptic cleft results in diminished activation of voltage-dependent NMDA-type glutamate receptors, shortening excitatory response duration and limiting temporal integration of inputs (Higley 2009). Thus, the pause in cholinergic interneuron firing would be predicted to enhance the efficacy and summation of glutamatergic inputs arriving during this period.
