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Effects of mGlu1 receptor blockade on anxiety-related behaviour in the rat lick suppression test.

Abstract：

RATIONALE:Group I metabotropic glutamate receptor antagonists, which block both the mGlu1 and mGlu5 receptors, have been shown to have anxiolytic effects in the lick suppression test in rats. OBJECTIVE:The anxiolytic potential of the selective mGlu1 antagonist 3,4-dihydro-2H-pyrano[2,3]beta-quinolin-7-yl)(cis-4-methoxycyclohexyl)methanone (JNJ16259685) was investigated and compared with the mGlu5 antagonist MPEP. METHODS:Anxiety-related behaviour was assessed in lick suppression and in the elevated zero maze in rats. Non-specific effects on pain threshold, water intake and locomotor activity were also measured. RESULTS:Acute administration of JNJ16259685 or MPEP increased the number of licks (lowest active dose 2.5 mg/kg IP for each compound). JNJ16259685 did not increase water intake or reduce acute pain threshold, suggesting that the anxiolytic-like properties are specific. However, acute administration decreased locomotor activity. The effects of chronic administration of JNJ16259685 over 14 days (5 mg/kg bid) on lick suppression were comparable to those seen after acute administration, arguing against development of behavioural tolerance or sensitisation. Yet, there was a tendency for an increase in locomotor activity after cessation of chronic treatment. Acute co-administration of both JNJ16259685 and MPEP had additive effects on the number of licks. No anxiolytic-like properties of JNJ16259685 were observed in the elevated zero maze. CONCLUSION:Our data suggest that the anxiolytic-like effects induced by group I metabotropic glutamate receptor antagonists are mediated through both mGlu1 and mGlu5 receptors. Rather than producing a general anxiolytic-like effect, the effects seen following mGlu1 antagonism seem task-dependent, as prominent effects were seen in a conflict procedure, but not in a task based on spontaneous exploration.

journal_name

Psychopharmacology (Berl)

journal_title

Psychopharmacology

authors

Steckler T,Lavreysen H,Oliveira AM,Aerts N,Van Craenendonck H,Prickaerts J,Megens A,Lesage AS

doi

10.1007/s00213-004-2056-7

subject

Has Abstract

pub_date

2005-04-01 00:00:00

pages

198-206

issue

eissn

0033-3158

issn

1432-2072

journal_volume

179

pub_type

杂志文章

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Effects of mGlu1 receptor blockade on anxiety-related behaviour in the rat lick suppression test.