title: Lack of persistent effects of ketamine in rodent models of depression.
abstract: BACKGROUND
  We investigated the immediate and enduring effects of ketamine in behavioral and neurochemical assays predictive of antidepressant activity.
  
  
  METHODS
  One week after a single administration of ketamine (50-160 mg/kg), otherwise experimentally naive rats and mice were tested either in the forced swim test (FST) or the tail suspension test (TST). Other mice were also tested twice in the FST: immediately and 2 weeks after a single dose (1.25-50 mg/kg) of ketamine. In the next series of experiments, rats treated for 2 weeks twice daily with ketamine (50 or 160 mg/kg) or desipramine (10 mg/kg) were challenged with apomorphine and scored for locomotor activity and assayed for the density of cortical beta-adrenoceptors. The latter test was also carried out in rats that had received a single dose of ketamine (50 mg/kg) 1 week before the assay. The antidepressant-like (FST) and locomotor effects of ketamine (50 mg/kg) and desipramine (10 mg/kg) were assessed after their chronic (2 weeks, twice daily) administration as well.
  
  
  RESULTS
  We report the lack of enduring antidepressant-like effect of ketamine in both rats and mice. A 2-week treatment with ketamine neither changed apomorphine-evoked locomotor hyperactivity nor did it decrease the density of cortical beta-adrenoceptors. However, some tolerance to the antidepressant-like effect of ketamine was noted in the FST, but it was accompanied by sensitization to its locomotor stimulatory effects.
  
  
  CONCLUSIONS
  These data indicate that ketamine neither produces enduring antidepressant-like effects in rodents nor does it display antidepressant-like behavioral or neurochemical effects after chronic treatment.
authors.affiliation: Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Kraków, Poland. nfpopik@cyf-kr.edu.pl
authors.forename: Piotr
authors.initials: P
authors.lastname: Popik
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kos
authors.forename: Magdalena
authors.initials: M
authors.lastname: Sowa-Kućma
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nowak
mesh_terms: D000818:Animals; D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001058:Apomorphine / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000523:psychology*; D003891:Desipramine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004361:Drug Tolerance; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D019417:Hindlimb Suspension / Q000523:psychology; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D013550:Swimming / Q000523:psychology
chemical_list: D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D018491:Dopamine Agonists; D018691:Excitatory Amino Acid Antagonists; D011943:Receptors, Adrenergic, beta; D007649:Ketamine; D001058:Apomorphine; D003891:Desipramine