Differential effects of MPEP and diazepam in tests of conditioned emotional response and Pavlovian-to-instrumental transfer suggests 'anxiolytic' effects are mediated by different mechanisms.
BACKGROUND
The selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) is reported to be anxiolytic in several animal models of anxiety, including the conditioned emotional response (CER) paradigm. Suppression of responding during conditioned stimulus (CS) presentation in CER may reflect behavioural competition between lever pressing and adopting a shock-avoidance posture, or it may alternatively reflect altered value of the food reward following its association with a footshock, thus reducing its ability to motivate responding. If this is the case, then drugs that reduce the CER may interfere with the mechanism by which CSs are able to motivate responding, rather than by reducing anxiety. The standard test of the ability of Pavlovian cues to motivate responding is the Pavlovian-to-instrumental transfer (PIT) paradigm and it has recently been suggested that CER may be 'negative PIT'.


METHODS
We compared the effect of MPEP (0, 3, 10 and 30 mg/kg) and diazepam (0, 1, 3 and 10 mg/kg) in CER and PIT.


RESULTS
Both MPEP and diazepam significantly reduced conditioned suppression in the CER paradigm. MPEP, but not diazepam, significantly reduced PIT.


CONCLUSIONS
The findings support the hypothesis that MPEP may reduce expression of anxiety in the CER paradigm by interfering with the way in which emotionally salient cues are able to affect behaviour, but do not support such an analysis of the effect of diazepam. Diazepam and MPEP may therefore achieve their effects in CER by influencing different psychological processes.
George
S A
SA
Department of Psychology, School of Life Sciences, University of Sussex, Falmer, Brighton, UK.
Hutson
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PH
Stephens
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DN
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D003463:Cues; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004644:Emotions / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005502:Food; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D008297:Male; D009042:Motivation; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors*
D014151:Anti-Anxiety Agents; D003975:Diazepam; D018691:Excitatory Amino Acid Antagonists; D011725:Pyridines; D018092:Kainic Acid Receptors; C121465:6-methyl-2-(phenylethynyl)pyridine