Differential effects of cholinergic drugs on discriminative cues and self-stimulation produced by electrical stimulation of the ventral tegmental area.

Cholinergic receptors have been shown to modulate a subset of discriminative cues produced by electrical stimulation of the ventral tegmental area (VTA) in rats. The present study identified the specific cholinergic receptor type modulating these electrical brain-stimulation (EBS) cues, and assessed whether these receptors also mediated the rewarding effects of VTA EBS. The EBS cues were enhanced by the acetylcholinesterase inhibitor physostigmine and the muscarinic receptor agonists pilocarpine and RS-86, whereas the nicotinic receptor agonist nicotine had no effect. The enhancing effects of pilocarpine or RS-86 were attenuated by the muscarinic antagonist scopolamine. The EBS cues were not affected when scopolamine was injected alone, although high doses disrupted discriminated responses. Intracranial self-stimulation (ICSS) rates were depressed by physostigmine and pilocarpine and increased by nicotine and scopolamine. These results indicated a facilitatory influence of muscarinic receptors on the EBS cues, and an inhibitory role in VTA ICSS. Nicotinic receptor activation did not affect the EBS cues, but facilitated ICSS. These differential effects of cholinergic receptor activation point to a dissociation of the specific EBS cues measured in this study from the rewarding effects of VTA stimulation.