Cholinergic and dopaminergic interactions alter attention and response inhibition in Long-Evans rats performing the 5-choice serial reaction time task

Abstract

Acetylcholine (ACh) neurotransmission is important for attention, while dopamine (DA) signaling modulates impulsive behavior. Prior studies have established an existing relationship between ACh and DA that mediates dopamine release in the prefrontal cortex of the brain in rats performing the 5-choice serial reaction time task (5-CSRTT). This study is aimed to identify cholinergic and dopaminergic interactions that govern attention and impulsive behavior, using adult Long-Evans rats of both sexes and a 5-CSRTT, with variable short and long cue delays. In Experiment 1, the effects of single cholinergic and dopaminergic drugs were evaluated on 5-CSRTT performance. Drugs like nicotinic ACh receptor (nAChR) agonist nicotine, amphetamine, and GBR12909 that increase the synaptic levels of ACh and DA respectively all increased impulsive behavior. In addition, amphetamine and GBR 12909 decreased attention while nicotine had no effect on attention. The antagonists mecamylamine, a general nAChR antagonist, flupenthixol a DA 1/2 receptor antagonist, and SCH 23390 a DA 1 receptor antagonist, all decreased impulsive behavior, with mixed effects on attention. In contrast, dihydro-β-erythroidine hydrobromide (DHBE), an α4β2 subunit-specific nAChR antagonist, had no significant effects on attention or impulsivity across doses administered. Eticlopride, a DA 2 receptor antagonist, decreased attention at the shortest cue delay but did not affect impulsivity. The acetylcholinesterase inhibitor donepezil decreased both attention and impulsive behavior. Subsequently in Experiment 2, effects of nicotine and amphetamine were determined after pretreatment with SCH 23390 or eticlopride. SCH 23390 attenuated the effects of nicotine and amphetamine to increase impulsivity, while eticlopride only attenuated the effect of nicotine on impulsivity. Minimal effects were seen on attention in the combination trials. This study confirms that dopamine D1 receptor plays an essential role in modulation of impulsive behavior, as measured by the 5-CSRTT. More importantly, it establishes that impulsive behavior is altered by interactions between cholinergic and dopaminergic neurotransmission.