title: Behavioral and cross sensitization after repeated exposure to modafinil and apomorphine in rats.
abstract: Repeated exposure to psychostimulant drugs has been known to produce behavioral sensitization, a phenomenon explicitly indexed by locomotion (LM) and stereotyped movements (SM). So far, no evidence has demonstrated that this phenomenon can be displayed following the administration of modafinil (MOD) in animal study. We, therefore, assessed the possibility of behavioral sensitization of MOD and a direct dopamine agonist, apomorphine (APO), and cross-sensitization of these two drugs with one other. Pretreatment with MOD (64 mg/kg) or APO (0.5 mg/kg or 1.0 mg/kg) for 10 consecutive days was followed by a short-term (3 days) or long-term (21 days) withdrawal. Rats were then challenged with the drug and reciprocally re-challenged with the counterpart drug. The results showed that following short-term and long-term washout periods, both MOD and APO successfully induced sensitization in LM and SM. There was no cross-sensitization; an even lesser magnitude in LM when MOD-sensitized rats were challenged with APO was observed. However, after both the short-term and long-term withdrawal periods, APO (1.0 mg/kg)-sensitized rats showed cross-sensitization in LM and SM to MOD (64 mg/kg) challenge. The magnitude of APO-MOD cross-sensitization was lesser than the behavioral sensitization induced by APO alone. Our results indicated behavioral sensitization could be induced in rats exposed to MOD. In addition, changes in dopaminergic receptor activities could be involved in cross-sensitization of APO to MOD but not vice versa.
authors.affiliation: Department of Physiology and Biophysics, Cardinal Tien Hospital, Taipei 114, Taiwan, Republic of China.
authors.forename: Shang-Tang
authors.initials: ST
authors.lastname: Chang
authors.forename: Che-Se
authors.initials: CS
authors.lastname: Tung
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lin
authors.forename: Chia-Hsin
authors.initials: CH
authors.lastname: Chuang
authors.forename: An-Rong
authors.initials: AR
authors.lastname: Lee
authors.forename: Yia-Ping
authors.initials: YP
authors.lastname: Liu
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D000077408:Modafinil; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D001058:Apomorphine; D000077408:Modafinil