A within-subjects microdialysis/behavioural study of the role of striatal acetylcholine in D1-dependent turning

Acquas, Elio; Fenu, Sandro; Loddo, P.; Chiara, G. Di

doi:10.1016/s0166-4328(99)00038-8

Cited by 6 publications

(4 citation statements)

References 35 publications

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“…A 2A antagonists have been shown to be efficacious against haloperidolinduced catalepsy [16,20,50] and showed positive effects in the forepaw stepping test in unilaterally 6-OHDA lesioned rats [51] and in the rotarod test [52]. However, most studies failed to demonstrate a significant effect of A 2A receptor antagonists on the level of contralateral rotation in lesioned rats in the absence of L-Dopa [14][15][16]53]. To our knowledge, this is the first time that the efficacy of A 2A receptor antagonists on motor activity has been systematically evaluated in unilaterally 6-OHDA-lesioned rats by measuring the general level of motor activity.…”

Section: Discussionmentioning

confidence: 99%

Unprecedented therapeutic potential with a combination of A2A/NR2B receptor antagonists as observed in the 6-OHDA lesioned rat model of Parkinson's disease

Michel

Downey

Nicolas

et al. 2016

Parkinsonism & Related Disorders

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Section: Discussionmentioning

confidence: 99%

Unprecedented therapeutic potential with a combination of A2A/NR2B receptor antagonists as observed in the 6-OHDA lesioned rat model of Parkinson's disease

Michel

Downey

Nicolas

et al. 2016

Parkinsonism & Related Disorders

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“…A 2A antagonists have been shown to be efficacious against haloperidol-induced catalepsy [16] , [20] , [50] and showed positive effects in the forepaw stepping test in unilaterally 6-OHDA lesioned rats [51] and in the rotarod test [52] . However, most studies failed to demonstrate a significant effect of A 2A receptor antagonists on the level of contralateral rotation in lesioned rats in the absence of L-Dopa [14] – [16] , [53] . To our knowledge, this is the first time that the efficacy of A 2A receptor antagonists on motor activity has been systematically evaluated in unilaterally 6-OHDA-lesioned rats by measuring the general level of motor activity.…”

Section: Discussionmentioning

confidence: 99%

Unprecedented Therapeutic Potential with a Combination of A2A/NR2B Receptor Antagonists as Observed in the 6-OHDA Lesioned Rat Model of Parkinson's Disease

et al. 2014

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In Parkinson's disease, the long-term use of dopamine replacing agents is associated with the development of motor complications; therefore, there is a need for non-dopaminergic drugs. This study evaluated the potential therapeutic impact of six different NR2B and A2A receptor antagonists given either alone or in combination in unilateral 6-OHDA-lesioned rats without (monotherapy) or with (add-on therapy) the co-administration of L-Dopa: Sch-58261+ Merck 22; Sch-58261+Co-101244; Preladenant + Merck 22; Preladenant + Radiprodil; Tozadenant + Radiprodil; Istradefylline + Co-101244. Animals given monotherapy were assessed on distance traveled and rearing, whereas those given add-on therapy were assessed on contralateral rotations. Three-way mixed ANOVA were conducted to assess the main effect of each drug separately and to determine whether any interaction between two drugs was additive or synergistic. Additional post hoc analyses were conducted to compare the effect of the combination with the effect of the drugs alone. Motor activity improved significantly and was sustained for longer when the drugs were given in combination than when administered separately at the same dose. Similarly, when tested as add-on treatment to L-Dopa, the combinations resulted in higher levels of contralateral rotation in comparison to the single drugs. Of special interest, the activity observed with some combinations could not be described by a simplistic additive effect and involved more subtle synergistic pharmacological interactions. The combined administration of A2A/NR2B-receptor antagonists improved motor behaviour in 6-OHDA rats. Given the proven translatability of this model such a combination may be expected to be effective in improving motor symptoms in patients.

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“…Adenosine acts through A 1 , A 2A , A 2B , and A 3 receptors, among which A 2A receptors are highly enriched in certain brain areas including striatum while less in other brain regions such as the cerebral cortex (Schiffmann et al 2007 ; Sihver et al 2009 ). In neurochemical studies it was showed that local or systemic activation of A 2A receptors in dorsal and ventral striatum enhanced the release of DA and glutamate (Golembiowska and Zylewska 1997 ; Popoli et al 1995 ; Quarta et al 2004 ; Tanganelli et al 2004 ) while stimulation of A 2A receptors in medial PFc reduced striatal DA release (Acquas et al 1999 ). On the other hand, the DA or glutamate release under control over A 2A receptors is not unequivocally established as either reduction (Quarta et al 2004 ), increase (Harper et al 2006 ), or no effect (Quarta et al 2004 ; Solinas et al 2002 ) was described following the local receptor blockade in the rat ventral and/or dorsal striatum.…”

Section: Introductionmentioning

confidence: 99%

Effects of intra-accumbal or intra-prefrontal cortex microinjections of adenosine 2A receptor ligands on responses to cocaine reward and seeking in rats

et al. 2018

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Rationale and objectivesMany studies indicated that adenosine via its A2A receptors influences the behavioral effects of cocaine by modulating dopamine neurotransmission. The hypothesis was tested that A2A receptors in the nucleus accumbens (NAc) or the prefrontral cortex (PFc) may modulate cocaine reward and/or cocaine seeking behavior in rats.MethodsThe effects of local bilateral microinjections of the selective A2A receptor agonist CGS 21680 or the A2A receptor antagonists KW 6002 and SCH 58261 were investigated on cocaine self-administration on reinstatement of cocaine seeking.ResultsThe intra-NAc shell, but not intra-infralimbic PFc, administration of CGS 21680 significantly reduced the number of active lever presses and the number of cocaine (0.25 mg/kg) infusions. However, tonic activation of A2A receptors located in the NAc or PFc did not play a role in modulating the rewarding actions of cocaine since neither KW 6002 nor SCH 58261 microinjections altered the cocaine (0.5 mg/kg) infusions. The intra-NAc but not intra-PFc microinjections of CGS 21680 dose- dependently attenuated the reinstatement of active lever presses induced by cocaine (10 mg/kg, i.p.) and the drug-associated combined conditioned stimuli using the subthreshold dose of cocaine (2.5 mg/kg, i.p.). On the other hand, the intra-NAc pretreatment with SCH 58261, but not with KW 6002, given alone evoked reinstatement of cocaine seeking behavior.ConclusionThe results strongly support the involvement of accumbal shell A2A receptors as a target, the activation of which exerts an inhibitory control over cocaine reward and cocaine seeking.

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A within-subjects microdialysis/behavioural study of the role of striatal acetylcholine in D1-dependent turning

Cited by 6 publications

References 35 publications

Unprecedented therapeutic potential with a combination of A2A/NR2B receptor antagonists as observed in the 6-OHDA lesioned rat model of Parkinson's disease

Unprecedented therapeutic potential with a combination of A2A/NR2B receptor antagonists as observed in the 6-OHDA lesioned rat model of Parkinson's disease

Unprecedented Therapeutic Potential with a Combination of A2A/NR2B Receptor Antagonists as Observed in the 6-OHDA Lesioned Rat Model of Parkinson's Disease

Effects of intra-accumbal or intra-prefrontal cortex microinjections of adenosine 2A receptor ligands on responses to cocaine reward and seeking in rats

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