Lack of persistent effects of ketamine in rodent models of depression.
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.
Popik
Piotr
P
Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Kraków, Poland. nfpopik@cyf-kr.edu.pl
Kos
Tomasz
T
Sowa-Kućma
Magdalena
M
Nowak
Gabriel
G
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
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