Effect of HD-23, a potent long acting cocaine-analog, on cocaine self-administration in rats.
BACKGROUND
"Agonist" therapy for drug addiction proposes that a long acting analog, with similar properties to the abused substance might serve as a useful therapeutic agent. HD-23 is a very long acting tropane analog that displays a neurochemical profile similar to cocaine.


OBJECTIVE
To determine, using self-administration procedures and three different schedules of reinforcement, the effect of HD-23 on rate of cocaine intake (fixed ratio), the effect of HD-23 on the motivation to respond (progressive ratio) and the time course of HD-23 pretreatment (discrete trials).


METHODS
Male Sprague-Dawley rats were implanted with chronically indwelling intravenous cannulae and trained to self-administer cocaine (1.5 mg/kg per infusion) on a fixed ratio schedule. After a stable baseline was established, separate groups of rats ( n=6-8) were given access to various doses of cocaine (0.37, 0.75, 1.5 or 3.0 mg/kg per injection) on a fixed ratio schedule during daily 3-h sessions, or to various doses of cocaine (0.18, 0.37, 0.75, 1.5 mg/kg per injection) on a progressive ratio schedule during daily 5-h sessions. A separate group of rats ( n=10) was tested using a discrete trials procedure; animals were given the opportunity to self-administer cocaine (1.5 mg/kg per injection) during 10-min trials which were initiated every 20 min throughout the day/night cycle.


RESULTS
On the FR schedule, pretreatment with HD-23 (1.0 mg/kg) decreased the rate of cocaine intake. HD-23 shifted the dose-response curve on the PR schedule to the left. On the discrete trials schedule, animals displayed a circadian pattern of drug intake; pretreatment with HD-23 significantly increased cocaine intake for about 8 h during the light phase when the probability of responding would otherwise have been very low. Animals pretreated with HD-23 displayed a high probability of cocaine self-administration for about 14 h.


CONCLUSIONS
The results are consistent with the idea that an acute pretreatment with the long-acting agonist, HD-23, augmented rather than diminished the motivation to self-administer cocaine.
Roberts
David C S
DC
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083, USA. dcsrobts@wfubmc.edu
Jungersmith
Kelly R
KR
Phelan
Rachel
R
Gregg
Timothy M
TM
Davies
Huw M L
HM
D000818:Animals; D016739:Behavior, Addictive / Q000523:psychology*; D003042:Cocaine / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D008297:Male; D009042:Motivation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012646:Self Administration
C112780:2-propanoyl-3-(2-naphthyl)-tropane; D003042:Cocaine