Rewarding brain stimulation: Role of tegmental cholinergic neurons that activate dopamine neurons.

Abstract

Cholinergic neurons of the pedunculopontine nucleus (Ch5) are believed to monosynaptically excite ventral tegmental dopamine neurons. Muscarinic blockers injected near dopamine cells block the rewarding effect of hypothalamic or dorsal tegmental rewarding brain stimulation (RBS) in rats. Because Ch5 cells are inhibited by muscarinic agonists, we injected muscarinic drugs unilaterally near Ch5 neurons to inhibit or disinhibit them. Carbachol raised thresholds for hypothalamic self-stimulation bilaterally by over 400%, whereas scopolamine reduced thresholds by 20%-80%. Pretreatment with either carbachol or scopolamine blocked the effect of the other drug, which suggests that both acted through the same receptors near Ch5 cells. Therefore, activation of Ch5 neurons is critical for hypothalamic RBS. A mechanism for the involvement of Ch5 neurons in drug rewards and antimuscarinic psychosis is also proposed.

Novel Therapeutic Strategies for Alcohol and Drug Addiction: Focus on GABA, Ion Channels and Transcranial Magnetic Stimulation

“…This important observation strongly indicates that the neural substrate of the ICSS behavior is hyperpolarized, or more refractory, in alcohol-dependent subjects as compared with non-alcoholic controls. As the neural substrate of ICSS (Yeomans, 1989;Yeomans et al, 1993) involves DA axons near the electrode, these results are complementary to those reported above and well fit with a hypofunction of DA neurons. These observations may suggest that 'boosting' DA neurons to produce more available DA in the synaptic cleft could alleviate some of the symptoms of addiction and alcoholism, thereby acquiring a therapeutic character.…”

Blockade of central nicotine acetylcholine receptor signaling attenuate ghrelin-induced food intake in rodents

“…Moreover, the ability of ghrelin administered into the LDTg to increase accumbal dopamine is attenuated by blockade of nAChRs in the VTA (Jerlhag et al, 2008). Collectively these data indicate that the socalled "cholinergic-dopaminergic reward link", a circuit conferring the incentive value of natural and artificial rewards (Yeomans et al, 1993, Lanca et al, 2000, Rada et al, 2000, Larsson and Engel, 2004, is a potential target for ghrelin's effects on the reward system.…”

Role of α1-Adrenoceptors of the Locus Coeruleus in Self-Stimulation of the Medial Forebrain Bundle

“…VTA neurons are also excited by MFB selfstimulation via cholinergic fibers arising in the laterodorsal and pedunculopontine tegmentum (Yeomans et al, 1993;Yeomans and Baptista, 1997). Thus, projections from the LC and pedunculopontine tegmentum might summate or synergize at the VTA to enhance self stimulation from the lateral hypothalamus.…”