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


CONCLUSIONS
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.
Steckler
Thomas
T
Johnson & Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium. tsteckle@prdbe.jnj.com
Lavreysen
Hilde
H
Oliveira
Ana M
AM
Aerts
Nancy
N
Van Craenendonck
Hansfried
H
Prickaerts
Jos
J
Megens
Anton
A
Lesage
Anne S J
AS
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*
D014151:Anti-Anxiety Agents; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1