当前位置： SCI文献检索 > NEUROSCIENCE期刊下所有文献 > The purinergic P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2'4'-disulphonic acid prevents both the acute locomotor effects of amphetamine and the behavioural sensitization caused by repeated amphetamine injections in rats.

The purinergic P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2'4'-disulphonic acid prevents both the acute locomotor effects of amphetamine and the behavioural sensitization caused by repeated amphetamine injections in rats.

Abstract：

:Repeated administration of amphetamine-like psychostimulants produce a progressive and long-lasting hypersensitivity to their behavioural effects known as behavioural sensitization. Previous studies have shown that administration of the purinergic P2 receptor agonist 2-methylthio ATP into the nucleus accumbens of rats raises the extracellular level of dopamine accompanied with enhanced locomotion in a similar manner. Furthermore, the quantitative EEG after application of 2-methylthio ATP or amphetamine was characterized by an elevation of the alpha1-power. However, purinergic P2 receptor antagonists decreased the basal level of dopamine in the NAc and in addition prevented the effects of 2-methylthio ATP. The purpose of the present study was to investigate, whether endogenous ATP acting via purinergic P2 receptors is involved in the process of amphetamine-induced sensitization. Rats were treated systemically for five successive days with d-amphetamine (1.5 mg/kg) and tested in an open field with respect to their locomotor response. The enhanced locomotor activity after the first injection of amphetamine was diminished by the previous intracerebroventricular application of the purinergic P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2'4'-disulphonic acid (PPADS; 0.6 nmol) (P<0.05). The challenge with a lower dose of amphetamine (0.75 mg/kg) produced an increased locomotion in comparison to the response after the first amphetamine application indicating the expression of a behavioural sensitization. Pretreatment with PPADS prior to each amphetamine administration prevented the increase of locomotor activity after the challenge with amphetamine (P<0.05). In summary, the present study demonstrates that PPADS blocks both the acute locomotor effects of amphetamine and the development of behavioural sensitization to the psychostimulant. We suggest that the activation of purinergic P2 receptors by endogenous ATP is necessary for the expression of these effects.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Kittner H,Krügel U,Illes P

doi

10.1016/s0306-4522(00)00555-8

keywords:

subject

Has Abstract

pub_date

2001-01-01 00:00:00

pages

241-3

issue

2

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(00)00555-8

journal_volume

102

pub_type

杂志文章

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