Attenuation of cocaine-seeking behaviour by the AMPA/kainate receptor antagonist CNQX in rats.
BACKGROUND
It has been suggested previously that conditioned effects on drug-seeking behaviour are in part mediated through glutamatergic neurotransmission.


OBJECTIVE
To optimise a second-order schedule of IV cocaine reinforcement in Wistar rats and investigate the effects of the systemic AMPA/kainate receptor antagonist CNQX on cocaine-seeking behaviour under this schedule.


METHODS
Free-feeding Wistar rats were trained to respond for an IV cocaine infusion (0.25 mg/infusion) under a FI15 min(FR7:S) schedule, whereby the completion of FR7 responses led to the presentation of a conditioned stimulus (CS). After two 15-min fixed intervals, rats were allowed to respond for cocaine under an FR4(FR7:S) second-order schedule for another 120 min. After acquisition of stable responding, the cocaine unit dose was increased to 0.50 mg/infusion. The effects of CNQX (0, 0.75, 1.5, and 3 mg/kg IP) on cocaine seeking were then examined using a within-subjects design.


RESULTS
Increasing the cocaine unit dose increased responding during the first and second intervals, with a decrease in the latency to the first CS. CNQX decreased the number of cocaine responses in a dose-dependent manner during the first 15-min cocaine-free interval, but did not affect cocaine responding during either the second interval or the latter part of the session under the FR4(FR7:S) schedule. In the locomotor activity test, reductions in rearing were produced by higher CNQX doses than those that attenuated significantly responding during the first fixed interval.


CONCLUSIONS
These results suggest that AMPA/kainate receptors are involved in mediation of cocaine-seeking behaviour controlled partly by cocaine-associated cues.
Bäckström
Pia
P
Department of Mental Health and Alcohol Research, National Public Health Institute, POB 33, 00251 Helsinki, Finland.
Hyytiä
Petri
P
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000523:psychology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors*; D012055:Reinforcement Schedule; D012646:Self Administration
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors