title: Prolonged daily exposure to i.v. cocaine results in tolerance to its stimulant effects.
abstract: We have previously shown that 1 h, but not 6 h, of daily access to i.v. cocaine induces a sensitized response to i.v. cocaine challenge after 14 days of withdrawal. Here we tried to replicate these results using an i.p. cocaine challenge and adding a group of animals that had 1 h daily access to cocaine, but maintained levels of administration comparable to that of saline animals (i.e. a Coc group). Since addiction-associated neuroadaptations are particularly long lasting, we also tested the response to cocaine challenge after a longer withdrawal period of 60 days. Rats had daily access to i.v. self-administered saline or cocaine for 1 h (Coc1h), or to cocaine for 6 h (Coc6h) over 8 days. Subsequently, after 14 days of withdrawal only Coc animals showed a sensitized locomotor response to cocaine challenge administered i.p. After 60 days of withdrawal, i.p. cocaine failed to produce a sensitized response in Coc1h animals and produced a tolerant response in Coc6h animals. The present data support the notion that 6 h of daily access to cocaine leads to different neuroadaptations than those resulting from 1 h of daily access to the drug. In addition, these data further demonstrate a dissociation between sensitization and addiction to cocaine.
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Psychology, University of California, Santa Barbara, CA 93106-9600, United States. shahar@psych.ucsb.edu
authors.forename: Osnat
authors.initials: O
authors.lastname: Ben-Shahar
authors.forename: Justin M
authors.initials: JM
authors.lastname: Moscarello
authors.forename: Beth
authors.initials: B
authors.lastname: Jacob
authors.forename: Meghan P
authors.initials: MP
authors.lastname: Roarty
authors.forename: Aaron
authors.initials: A
authors.lastname: Ettenberg
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants; D003042:Cocaine / Q000009:adverse effects / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004361:Drug Tolerance; D005502:Food; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000523:psychology
chemical_list: D000697:Central Nervous System Stimulants; D003042:Cocaine