Steady-dose and escalating-dose "binge" administration of cocaine alter expression of behavioral stereotypy and striatal preprodynorphin mRNA levels in rats.
This study examined the effects of chronic (14-day) steady-dose and escalating-dose "binge" pattern cocaine administration on striatal preprodynorphin (ppDyn) mRNA levels and behavioral stereotypies. Animals in the steady-state and escalating groups received cocaine in a "binge" pattern (three equal injections starting 30 min following the start of the daily light cycle, separated by 1 h). The dose of cocaine in the "steady-dose" group was 15 mg/kg/injection and remained constant throughout the study. The escalating group received 15 mg/kg/injection on days 1-3, 20 mg/kg/injection on days 4-6, 25 mg/kg/injection on days 7-9 and 30 mg/kg/injection thereafter, for a maximum daily dose of 90 mg/kg. Levels of ppDyn mRNA were determined by solution hybridization. Cocaine significantly affected body weight. Both steady-dose and escalating-dose "binge" cocaine administration resulted in expression of behavioral stereotypy and induced intense, rapid head movements which were dose- and time-dependent. Cocaine, independent of dose, increased ppDyn mRNA levels in the caudate putamen (CPu), but not in the nucleus accumbens (NAc). These data suggest that the ppDyn response to cocaine in the CPu is not dose-dependent or that it has reached a maximal level at the 45 mg/kg daily dose.
Schlussman
Stefan D
SD
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10021, USA. schluss@mail.rockfeller.edu
Zhou
Yan
Y
Bailey
Alexis
A
Ho
Ann
A
Kreek
Mary Jeanne
MJ
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004399:Dynorphins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013239:Stereotyped Behavior / Q000187:drug effects*; D013997:Time Factors
D018765:Dopamine Uptake Inhibitors; D011498:Protein Precursors; D012333:RNA, Messenger; C036448:pre-prodynorphin; D004399:Dynorphins; D003042:Cocaine