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Modulation of mGlu5 reduces rewarding associative properties of nicotine via changes in mesolimbic plasticity: Relevance to comorbid cigarette smoking in psychosis

Peeters, Loren D. ; Wills, Liza J. ; Cuozzo, Anthony M. ; Ivanich, Kira L. ; Turney, Seth E. ; Bullock, Luke P. ; Price, Robert M. ; Gass, Justin T. ; Brown, Russell W.

Pharmacology, biochemistry and behavior, 2024-06, Vol.239, p.173752, Article 173752 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Modulation of mGlu5 reduces rewarding associative properties of nicotine via changes in mesolimbic plasticity: Relevance to comorbid cigarette smoking in psychosis
Autor: Peeters, Loren D. ; Wills, Liza J. ; Cuozzo, Anthony M. ; Ivanich, Kira L. ; Turney, Seth E. ; Bullock, Luke P. ; Price, Robert M. ; Gass, Justin T. ; Brown, Russell W.
Assuntos: Adolescence ; Allosteric Regulation - drug effects ; Animals ; Animals, Newborn ; Benzamides - pharmacology ; Benzamides - therapeutic use ; Cigarette Smoking ; Conditioned place preference ; Female ; Limbic System - drug effects ; Limbic System - metabolism ; Male ; mGlu5 ; Neuronal Plasticity - drug effects ; Nicotine ; Nicotine - pharmacology ; Nucleus Accumbens - drug effects ; Nucleus Accumbens - metabolism ; Plasticity ; Psychosis ; Psychotic Disorders - drug therapy ; Psychotic Disorders - metabolism ; Pyrazoles - pharmacology ; Quinpirole - pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, Metabotropic Glutamate 5 - metabolism ; Reward
É parte de: Pharmacology, biochemistry and behavior, 2024-06, Vol.239, p.173752, Article 173752
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Descrição: Antipsychotic medications that are used to treat psychosis are often limited in their efficacy by high rates of severe side effects. Treatment success in schizophrenia is further complicated by high rates of comorbid nicotine use. Dopamine D2 heteroreceptor complexes have recently emerged as targets for the development of more efficacious pharmaceutical treatments for schizophrenia. The current study sought to explore the use of the positive allosteric modulator of the mGlu5 receptor 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) as a treatment to reduce symptoms related to psychosis and comorbid nicotine use. Neonatal treatment of animals with the dopamine D2-like receptor agonist quinpirole (NQ) from postnatal day (P)1–21 produces a lifelong increase in D2 receptor sensitivity, showing relevance to psychosis and comorbid tobacco use disorder. Following an 8-day conditioning paradigm, brain tissue in the mesolimbic pathway was analyzed for several plasticity markers, including brain derived neurotrophic factor (BDNF), phosphorylated p70 ribosomal S6 kinase (phospho-p70S6K), and cadherin-13 (Cdh13). Pretreatment with CDPPB was effective to block enhanced nicotine conditioned place preference observed in NQ-treated animals. Pretreatment was additionally effective to block the nicotine-induced increase in BDNF and sex-dependent increases in cadherin-13 in the ventral tegmental area (VTA), as well as increased phospho-p70S6K in the nucleus accumbens (NAcc) shell found in NQ-treated animals. In conjunction with prior work, the current study suggests positive allosteric modulation of the mGlu5 receptor, an emerging target for schizophrenia therapeutics, may be effective for the treatment of comorbid nicotine abuse in psychosis. [Display omitted] •Treatment success in schizophrenia is impeded by high rates of nicotine use.•A2A-D2-mGlu5 receptor complexes are an emerging treatment target for psychosis.•Neonatal quinpirole rodent model produces increased D2 receptor sensitivity.•In model, modulation of mGlu5 blocks enhanced nicotine conditioned place preference.•Modulation also blocks enhanced plasticity response to nicotine in quinpirole model.
Editor: United States: Elsevier Inc
Idioma: Inglês

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Modulation of mGlu5 reduces rewarding associative properties of nicotine via changes in mesolimbic plasticity: Relevance to comorbid cigarette smoking in psychosis

Peeters, Loren D. ; Wills, Liza J. ; Cuozzo, Anthony M. ; Ivanich, Kira L. ; Turney, Seth E. ; Bullock, Luke P. ; Price, Robert M. ; Gass, Justin T. ; Brown, Russell W.

United States: Elsevier Inc

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