Chronic Treatment with Clozapine, but Not Haloperidol, Increases Striatal Ecto-5′-Nucleotidase Activity in Rats

Lara, Diogo R.; Vianna, Mônica Ryff Moreira Roca; Paris, Fernanda de; Quevedo, Joao L De; Oses, Jean Pierre; Battastini, Ana Maria Oliveira; Sarkis, João José Freitas; Souza, Diogo O.

doi:10.1159/000054925

Cited by 16 publications

(16 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although both drugs reduced the peak response rate, haloperidol reduced and clozapine increased the "motivational" parameter of the operant behavior in a manner similar to D-amphetamine. These findings are consistent with a reduction of reinforcer efficacy produced by haloperidol and an increase in reinforcer efficacy produced by clozapine (Cilia et al 2001;Lara et al 2001).…”

Section: Introductionsupporting

confidence: 85%

Differential effects of clozapine and haloperidol on interval timing in the supraseconds range

MacDonald

Meck

2005

Psychopharmacology

View full text Add to dashboard Cite

The effects of clozapine (0.6, 1.2, and 2.4 mg/kg) and haloperidol (0.03, 0.06, and 0.12 mg/kg) on the timing of 10, 30, and 90-s intervals were characterized in rats. Each drug's effect on timing behavior was assessed following intraperitoneal injections using a variant of the peak-interval procedure. Although haloperidol proportionately shifted peak times rightward in a manner consistent with a decrease in clock speed, clozapine exerted the opposite effect and proportionately shifted peak times leftward in a manner consistent with an increase in clock speed. These results support the proposal that typical antipsychotic drugs such as haloperidol and atypical antipsychotic drugs such as clozapine exert differential effects on dopaminergic, serotonergic, and glutamatergic systems within the cortex and striatum, two brain regions shown to be crucial for interval timing.

show abstract

Section: Introductionsupporting

confidence: 85%

Differential effects of clozapine and haloperidol on interval timing in the supraseconds range

MacDonald

Meck

2005

Psychopharmacology

View full text Add to dashboard Cite

show abstract

“…Moreover, striatal dopamine release is under tonic inhibition by adenosine acting on presynaptic A 1 receptors [216,217], which is also in line with the increased release of dopamine in schizophrenia [218]. Finally, it was observed that the ability of clozapine (an atypical anti-psychotic, an and to a lesser extent haloperidol) to induced c-fos expression is blocked by A 2A receptor antagonists [219] and this anti-psychotic also affected key pathways of formation of ATP-derived adenosine acting on A 2A receptors, the ecto-nucleotidase pathway [220]. Altogether, these observations are consistent with the possibility that the manipulation of A 2A receptor might help restore an adequate dopaminergic signalling.…”

Section: Adenosine a 2a Receptors And Schizophreniamentioning

confidence: 66%

Potential Therapeutic Interest of Adenosine A2A Receptors in Psychiatric Disorders

Cunha¹,

Ferré²,

Vaugeois³

et al. 2008

CPD

176

149

View full text Add to dashboard Cite

The interest on targeting adenosine A 2A receptors in the realm of psychiatric diseases first arose based on its tight physical and functional interaction with dopamine D 2 receptors. However, the role of central A 2A receptors is now viewed as much broader than just controlling D 2 receptor function. Thus, there is currently a major interest in the ability of A 2A receptors to control synaptic plasticity at glutamatergic synapses. This is due to a combined ability of A 2A receptors to facilitate the release of glutamate and the activation of NMDA. Therefore, A 2A receptors are now conceived as a normalizing device promoting adequate adaptive responses in neuronal circuits, a role similar to that fulfilled, in essence, by dopamine. This makes A 2A receptors a particularly attractive target to manage psychiatric disorders since adenosine may act as go-between glutamate and dopamine, two of the key players in mood processing. Furthermore, A 2A receptors also control glia function and brain metabolic adaptation, two other emerging mechanisms to understand abnormal processing of mood, and A 2A receptors are an important player in controlling the demise of neurodegeneration, considered an amplificatory loop in psychiatric disorders. Current data only provide an indirect confirmation of this putative role of A 2A receptors, based on the effects of caffeine (an antagonist of both A 1 and A 2A receptors) in psychiatric disorders. However, the introduction of A 2A receptors in clinics as antiparkinsonian agents is hoped to bolster our knowledge on the role of A 2A receptors in mood disorders in the near future.

show abstract

“…Increased serum 5'NT (enhanced AMP hydrolysis by e.g., glycosylphosphatidyl-inositol anchored and mainly soluble extracellular form of e5'NT) [82,200] activity have also been shown in a chronic animal model of electroconvulsive shock [339], in patients with epilepsy and in clozapinetreated schizophrenic patients [72,73] and in pentylenetetrazol-induced seizures [74,75]. Moreover, increased e5'NT activity has also been demonstrated in the rat striatum after chronic clozapine treatment [340], in different rat models of epilepsy evoked by administration of pentylenetetrazol, kainic acid and pilocarpine [76][77][78] and in a rat model of Parkinson's disease [71]. Furthermore, 3-mercaptopropionic acid induced seizures, which increased e5'NT activity in the rat cerebellum [341].…”

Section: Modulation Of 5'-nucleotidase Activity: a New Promising Thermentioning

confidence: 99%

5'-Nucleotidases, Nucleosides and their Distribution in the Brain: Pathological and Therapeutic Implications

Kovács

Dobolyi

Kékesi

et al. 2013

CMC

View full text Add to dashboard Cite

Elements of the nucleoside system (nucleoside levels, 5'-nucleotidases (5'NTs) and other nucleoside metabolic enzymes, nucleoside transporters and nucleoside receptors) are unevenly distributed in the brain, suggesting that nucleosides have region-specific functions in the human brain. Indeed, adenosine (Ado) and non-Ado nucleosides, such as guanosine (Guo), inosine (Ino) and uridine (Urd), modulate both physiological and pathophysiological processes in the brain, such as sleep, pain, memory, depression, schizophrenia, epilepsy, Huntington's disease, Alzheimer's disease and Parkinson's disease. Interactions have been demonstrated in the nucleoside system between nucleoside levels and the activities of nucleoside metabolic enzymes, nucleoside transporters and Ado receptors in the human brain. Alterations in the nucleoside system may induce pathological changes, resulting in central nervous system (CNS) diseases. Moreover, several CNS diseases such as epilepsy may be treated by modulation of the nucleoside system, which is best achieved by modulating 5'NTs, as 5'NTs exhibit numerous functions in the CNS, including intracellular and extracellular formation of nucleosides, termination of nucleoside triphosphate signaling, cell adhesion, synaptogenesis and cell proliferation. Thus, modulation of 5'NT activity may be a promising new therapeutic tool for treating several CNS diseases. The present article describes the regionally different activities of the nucleoside system, demonstrates the associations between these activities and 5'NT activity and discusses the therapeutic implications of these associations.

show abstract

Chronic Treatment with Clozapine, but Not Haloperidol, Increases Striatal Ecto-5′-Nucleotidase Activity in Rats

Cited by 16 publications

References 26 publications

Differential effects of clozapine and haloperidol on interval timing in the supraseconds range

Differential effects of clozapine and haloperidol on interval timing in the supraseconds range

Potential Therapeutic Interest of Adenosine A2A Receptors in Psychiatric Disorders

5'-Nucleotidases, Nucleosides and their Distribution in the Brain: Pathological and Therapeutic Implications

Contact Info

Product

Resources

About

Chronic Treatment with Clozapine, but Not Haloperidol, Increases Striatal Ecto-5′-Nucleotidase Activity in Rats

Cited by 16 publications

References 26 publications

Differential effects of clozapine and haloperidol on interval timing in the supraseconds range

Differential effects of clozapine and haloperidol on interval timing in the supraseconds range

Potential Therapeutic Interest of Adenosine A2A Receptors in Psychiatric Disorders

5&#39;-Nucleotidases, Nucleosides and their Distribution in the Brain: Pathological and Therapeutic Implications

Contact Info

Product

Resources

About

5'-Nucleotidases, Nucleosides and their Distribution in the Brain: Pathological and Therapeutic Implications