Abstract
Cholinergic input to the ventral tegmental area (VTA) is known to contribute to reward. Although it is known that the pedunculopontine tegmental nucleus (PPTg) provides an important source of excitatory input to the dopamine system, the specific role of PPTg cholinergic input to the VTA in cocaine reward has not been previously determined. We used a diphtheria toxin conjugated to urotensin-II (Dtx::UII), the endogenous ligand for urotensin-II receptors expressed by PPTg cholinergic but not glutamatergic or GABAergic cells, to lesion cholinergic PPTg neurons. Dtx::UII toxin infusion resulted in the loss of 95.78 (±0.65)% of PPTg cholinergic cells but did not significantly alter either cocaine or heroin self-administration or the development of cocaine or heroin conditioned place preferences. Thus, cholinergic cells originating in PPTg do not appear to be critical for the rewarding effects of cocaine or of heroin.
Highlights
The dopaminergic neurons of the midbrain are important for the rewarding effects of cocaine [1,2]
Our results indicate that pedunculopontine tegmental (PPTg) cholinergic function is not critical for the rewarding effects of either agent
Despite previous evidence implicating cholinergic input to the ventral tegmental area (VTA) in cocaine reward and in brain stimulation reward, neartotal loss of PPTg cholinergic neurons failed to significantly alter self-administration of cocaine or heroin or to alter the place preferences established with these drugs; the present data suggest that the rewarding effects of neither cocaine nor heroin depends
Summary
The dopaminergic neurons of the midbrain are important for the rewarding effects of cocaine [1,2] They receive inputs from a number of brain regions [3,4], and they respond to primary rewards and to the peripheral stimuli that predict primary rewards [5]. There are only two known sources of cholinergic input to the midbrain dopamine neurons: the pedunculopontine tegmental (PPTg) and laterodorsal tegmental (LDTg) nuclei [9,10]. Electrical stimulation of the PPTg or LDTg induces a tri-phasic pattern of dopamine efflux in the dorsal striatum or nucleus accumbens, respectively, and actions of acetylcholine at nicotinic and muscarinic cholinergic receptors in the VTA and SNc each contribute to mesopontine excitation of the dopamine system [12,13,14,15]
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