Long-lasting decreases in cocaine-reinforced behavior following treatment with the cholinesterase inhibitor tacrine in rats selectively bred for drug self-administration.
Tacrine is a centrally acting, reversible cholinesterase inhibitor that increases synaptic levels of acetylcholine (ACh) and can potentiate the actions of dopamine (DA). The present study was conducted to evaluate effects of tacrine on cocaine-reinforced responding in a rat line selectively bred for high levels of drug self-administration (the HS line). HS rats self-administered different doses of cocaine under a fixed-ratio-5 (FR-5) schedule. Over a four-day period, vehicle or tacrine (1.0, 3.2, or 10 mg/kg-day) was infused when animals were maintained in home cages (21 h per day). Tacrine dose-dependently decreased cocaine self-administration. Actions of tacrine differed for self-administration that was initiated within 20 min of pretreatment (described as early sessions), and for self-administration that occurred between one and three days after administration of tacrine was discontinued (late sessions). Tacrine's potency for attenuating self-administration during late sessions was greater for cocaine- relative to food-reinforcement in HS rats, and for HS relative to outbred rats. In a subset of tacrine-treated HS rats, cocaine self-administration was persistently attenuated by more than 80% from pretreatment baseline levels over a one-week period during which no further tacrine was administered. In summary, pretreatment with tacrine can produce a long-lasting attenuation of cocaine-reinforced responding.
Grasing
Kenneth
K
Substance Abuse Research Laboratory, 151, Kansas City Veterans Affairs Medical Center, 4801 Linwood Boulevard, Kansas City, MO 64128, USA. kgrasing@kumc.edu
He
Shuangteng
S
Yang
Yungao
Y
D000465:Algorithms; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001947:Breeding; D018678:Cholinergic Agents / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000235:genetics; D003216:Conditioning, Operant; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005508:Food Deprivation; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012646:Self Administration; D012727:Sex Characteristics; D013045:Species Specificity; D013619:Tacrine / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors
D018678:Cholinergic Agents; D002800:Cholinesterase Inhibitors; D018765:Dopamine Uptake Inhibitors; D013619:Tacrine; D003042:Cocaine