Effects on cocaine and food self-administration of (+)-HA-966, a partial agonist at the glycine/NMDA modulatory site, in rats.
BACKGROUND
(+)-HA-966, a partial agonist at the glycine/NMDA modulatory site, significantly reduced i.v. cocaine self-administration in a fixed-ratio (FR) schedule. Since this effect was observed studying only one dose of cocaine and considering the characteristic bell-shaped curve generated by cocaine in self-administration studies under FR schedules, the precise nature of the effect is not clear.


OBJECTIVE
To identify the nature of the effect of (+)-HA-966 on cocaine self-administration under fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement.


METHODS
Rats were prepared with i.v. catheters and trained to self-administer cocaine. In the first experiment three doses of (+)-HA-966 (10, 30 and 100 microg/5 microl i.c.v.) were evaluated for their effects on 0.25 mg/0.1 ml per infusion cocaine self-administration on FR1 with 20-s time-out (TO). Next, 30 microg/5 microl i.c.v. (+)-HA-966 was evaluated as pretreatment on a complete dose-response for cocaine self-administration. In a third experiment the effect of the same dose was evaluated on cocaine or food self-administered on the PR schedule.


RESULTS
(+)-HA-966 at doses of 10 or 30 microg reduced cocaine self-administration in an FR1 schedule during the first hour interval of the 2-h session. This partial agonist at the glycine/NMDA modulatory site also reduced the number of injections of cocaine earned during the first hour of the session but not the final ratio reached under a PR schedule. However, under this schedule (+)-HA-966 also reduced operant responding for food reinforcement.


CONCLUSIONS
(+)-HA-966 reduced responding maintained by cocaine or food. Whether (+)-HA-966 induces a general motivational rather than a performance deficit, leading to reduced responding for either cocaine and food, is unclear.
Cervo
Luigi
L
Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milan, Italy. cervo@marionegri.it
Cocco
Arianna
A
Carnovali
Francesco
F
D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage*; D005502:Food; D005998:Glycine / Q000378:metabolism; D008297:Male; D016202:N-Methylaspartate / Q000378:metabolism; D011760:Pyrrolidinones / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration; D013997:Time Factors
D018765:Dopamine Uptake Inhibitors; D018690:Excitatory Amino Acid Agonists; D011760:Pyrrolidinones; D016202:N-Methylaspartate; C001369:1-hydroxy-3-amino-2-pyrrolidone; D003042:Cocaine; D005998:Glycine