Modulation of dopamine efflux in the nucleus accumbens after cholinergic stimulation of the ventral tegmental area in intact, pedunculopontine tegmental nucleus-lesioned, and laterodorsal tegmental nucleus-lesioned rats

Blaha, Charles D.; Allen, L.; Das, Sheela; Inglis, Wendy L.; Latimer, Mary P.; Vincent, Steven R.; Winn, Philip

doi:10.1523/jneurosci.16-02-00714.1996

Cited by 193 publications

(140 citation statements)

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“…In this study, caudate was examined as a representative region of striatum for measuring changes in high affinity neuronal nicotinic receptor binding in control smokers and schizophrenic subjects. Caudate, as well as cortex, showed a reduced level of nicotinic receptor upregulation in schizophrenics, compared to control subjects, suggesting that cholinergic modulation of dopaminergic neurotransmission might be affected in schizophrenia (Grenhoff and Svensson 1988;Rapier et al 1990;Rowell 1995;Blaha et al 1996;Pidoplichko et al 1997). It is also interesting to note that schizophrenics demonstrated age related changes in neuronal nicotinic receptor numbers in both cortex and hippocampus, whereas control subjects demonstrated changes only in the cortex.…”

Section: Discussionmentioning

confidence: 96%

Abnormal Regulation of High Affinity Nicotinic Receptors in Subjects with Schizophrenia

Breese

2000

Neuropsychopharmacology

306

215

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Previous studies have suggested that an abnormality in neuronal nicotinic acetylcholine receptor expression or function may be involved in the neuropathophysiology of schizophrenia. [ 3 H]-nicotine and [ 3 H]-epibatidine binding were compared in postmortem brain from control and schizophrenic subjects with varying smoking histories. In control subjects, increased receptor binding was seen in hippocampus, cortex, and caudate with increasing tobacco use. In contrast, schizophrenic smokers had reduced nicotinic receptor levels in these brain regions compared to control smokers. Chronic haloperidol and nicotine treatment, in the rat, was used to assess neuroleptic effects on receptor up-regulation by nicotine. A significant increase in cortical nicotinic receptors was seen in both nicotine treated as well as haloperidol and nicotine co-treated animals, suggesting that the abnormal regulation of high affinity neuronal nicotinic receptors in schizophrenics followingPrevious studies have shown that high affinity nicotinic receptor numbers increase in the brains of human subjects who smoke (Benwell et al. 1988;Breese et al. 1997a;Court et al. 1998). This increase was shown to be dosedependent, based on the number of cigarettes smoked at death, and was reversible, with binding levels returning to control values in subjects who had quit smoking for at least two months prior to death (Breese et al. 1997a). The up-regulation of receptor numbers does not appear to be under transcriptional regulation (Marks et al. 1992). Rather, the increases may be related to changes in receptor turnover based on receptor desensitization, subunit composition, secondary structural changes in the receptor, or to modification of the receptor by protein kinases (Peng et al. 1994;Baenziger and Chew 1997;Eilers et al. 1997;Flores et al. 1997;Hsu et al. 1997;Xiao et al. 1998;Fenster et al. 1999).In spite of the high degree of nicotine self-administration in schizophrenics (Lohr and Flynn 1992;Ziedonis et al. 1994;de Leon et al. 1995), few studies have examined the effect of smoking or neuroleptic treatment on nicotinic receptor regulation in this disease (Dalack et al. 1998). It has been suggested that nicotine self-administration in schizophrenics may control a neuronal deficit. In this regard, it has been shown that abnormal electro- NO . 4 physiological and eye-tracking deficits can be normalized by cigarette smoking or nicotine administration (Adler et al. 1992(Adler et al. , 1993Olincy et al. 1998). Smoking may also alleviate neuroleptic-induced extrapyramidal side effects (Decina et al. 1990;Goff et al. 1992;Sandyk 1993). Nicotine use increases haloperidol metabolism (Jann et al. 1986;Miller et al. 1990), requiring patients that smoke to take higher doses than non-smoking schizophrenics, often further increasing their smoking behavior (McEvoy et al. 1995). Interestingly, clozapine, which does not induce the motor dysfunctions seen with typical neuroleptics, reduces smoking behavior (George et al. 1995) and normalizes the electrophysiologi...

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Section: Discussionmentioning

confidence: 96%

Abnormal Regulation of High Affinity Nicotinic Receptors in Subjects with Schizophrenia

Breese

2000

Neuropsychopharmacology

306

215

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“…In experiments carried out in vivo, cholinesterase inhibition in VTA was reported to augment DA release in the NAcc (Blaha et al, 1996). One interpretation of this data is that endogenous ACh transmission in the VTA activates the DA system.…”

Section: Disinhibition Of Vta Da Neurons and Rewardmentioning

confidence: 96%

“…The vast majority of the cholinergic neurons in the laterodorsal tegmental and the pedunculopontine nuclei project to GABA neurons in the VTA (Garzón et al, 1999). Therefore, the in vivo application of the cholinesterase inhibitor in the VTA by Blaha et al (1996), which was maintained for several hours, may induce increased DA levels in the NAcc by disinhibition of VTA DA neurons due to nAChR desensitization on GABA neurons.…”

Section: Disinhibition Of Vta Da Neurons and Rewardmentioning

confidence: 99%

Cellular and synaptic mechanisms of nicotine addiction

2002

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ABSTRACT:The tragic health effects of nicotine addiction highlight the importance of investigating the cellular mechanisms of this complex behavioral phenomenon. The chain of cause and effect of nicotine addiction starts with the interaction of this tobacco alkaloid with nicotinic acetylcholine receptors (nAChRs). This interaction leads to activation of reward centers in the CNS, including the mesoaccumbens DA system, which ultimately leads to behavioral reinforcement and addiction. Recent findings from a number of laboratories have provided new insights into the biologic processes that contribute to nicotine self-administration.Examination of the nAChR subtypes expressed within the reward centers has identified potential roles for these receptors in normal physiology, as well as the effects of nicotine exposure. The high nicotine sensitivity of some nAChR subtypes leads to rapid activation followed in many cases by rapid desensitization. Assessing the relative importance of these molecular phenomena in the behavioral effects of nicotine presents an exciting challenge for future research efforts.

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“…36 In addition, both systems do not function in isolation but closely interact with each other and with other neurotransmitter systems including dopamine, glutamate and GABA. [37][38][39][40][41] The interactions between the muscarinic cholinergic system and the nicotinic cholinergic system as well as other neurotransmitter systems are complex and bi-directional. Given the central role of dopamine in schizophrenia, the interactions between the muscarinic cholinergic system and the dopaminergic system will be reviewed in more detail.…”

Section: Cholinergic Neurotransmissionmentioning

confidence: 99%

Towards a muscarinic hypothesis of schizophrenia

Raedler

Bymaster

Tandon³

et al. 2006

Mol Psychiatry

250

211

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Although the neurotransmitter dopamine plays a prominent role in the pathogenesis and treatment of schizophrenia, the dopamine hypothesis of schizophrenia fails to explain all aspects of this disorder. It is increasingly evident that the pathology of schizophrenia also involves other neurotransmitter systems. Data from many streams of research including preclinical and clinical pharmacology, treatment studies, post-mortem studies and neuroimaging suggest an important role for the muscarinic cholinergic system in the pathophysiology of schizophrenia. This review will focus on evidence that supports the hypothesis that the muscarinic system is involved in the pathogenesis of schizophrenia and that muscarinic receptors may represent promising novel targets for the treatment of this disorder.

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Modulation of dopamine efflux in the nucleus accumbens after cholinergic stimulation of the ventral tegmental area in intact, pedunculopontine tegmental nucleus-lesioned, and laterodorsal tegmental nucleus-lesioned rats

Cited by 193 publications

References 53 publications

Abnormal Regulation of High Affinity Nicotinic Receptors in Subjects with Schizophrenia

Abnormal Regulation of High Affinity Nicotinic Receptors in Subjects with Schizophrenia

Cellular and synaptic mechanisms of nicotine addiction

Towards a muscarinic hypothesis of schizophrenia

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