Ionotropic and Metabotropic Glutamate Receptor Antagonism
Attenuates Cue-Induced Cocaine Seeking

by
Backstrom P, Hyytia P.
1Department of Mental Health and Alcohol Research,
National Public Health Institute,
Helsinki, Finland
Neuropsychopharmacology. 2005 Aug 3;


ABSTRACT

Neuroanatomical and pharmacological evidence implicates glutamate transmission in drug-environment conditioning that partly controls drug seeking and relapse. Glutamate receptors could be targets for pharmacological attenuation of the motivational properties of drug-paired cues and for relapse prevention. The purpose of the present study was therefore to investigate the involvement of ionotropic and metabotropic glutamate receptor subtypes in cue-induced reinstatement of cocaine-seeking behavior. Rats were trained to self-administer cocaine using a second-order schedule of reinforcement (FR4(FR5:S)) under which a compound stimulus (light and tone) associated with cocaine infusions was presented contingently. Following extinction, the effects of the competitive NMDA receptor antagonist CGP 39551 (0, 2.5, 5, 10 mg/kg intraperitoneally (i.p.)), two competitive AMPA/kainate antagonists, CNQX (0, 0.75, 1.5, 3 mg/kg i.p.) and NBQX (0, 1.25, 2.5, 5 mg/kg i.p.), the NMDA/glycine site antagonist L-701,324 (0, 0.63, 1.25, 2.5 mg/kg i.p.), and the mGluR5 antagonist MPEP (0, 1.25, 2.5, 5 mg/kg i.p.) on cue-induced reinstatement of cocaine seeking were examined. The AMPA/kainate receptor antagonists CNQX and NBQX, the NMDA/glycine site antagonist L-701,324, and the mGluR5 antagonist MPEP attenuated significantly cue-induced reinstatement. The NMDA antagonist CGP 39551 failed to affect reinstatement. Additional control experiments indicated that attenuation of cue-induced reinstatement by CNQX, NBQX, L-701,324, and MPEP was not accompanied by significant suppression of spontaneous locomotor activity. These results suggest that conditioned influences on cocaine seeking depend on glutamate transmission. Accordingly, drugs with antagonist properties at various glutamate receptor subtypes could be useful in prevention of relapse induced by conditioned stimuli


NR2B
MGlu5
History
Acupuncture
Crack and crime
Dopaminergic flies?
Dopaminergic agents
The coke-craving brain
Monoamines, cocaine and rats
Freebasing flies go hyperkinetic
Glutamate, dopamine and cocaine addiction
Glutamate transmission and addiction to cocaine

01 02 03 04 05 06 07 08 09 10 11 12
13 14 15 16 17 18 19 20 21 22 23 24


Refs
HOME
HedWeb
cannabis-marijuana.com
Future Opioids
BLTC Research
Wirehead Hedonism
Paradise-Engineering
Utopian Pharmacology
The Hedonistic Imperative
When Is It Best to Take Crack Cocaine?

swan image
The Good Drug Guide
The Responsible Parent's Guide To
Healthy Mood Boosters For All The Family