Effects of ketamine and pentobarbital on noradrenaline release from the medial prefrontal cortex in rats.
OBJECTIVE
To determine the effects of ketamine and pentobarbital on noradrenaline release from the medial prefrontal cortex.


METHODS
In 14 male Wistar rats, a microdialysis probe with a 2 mm long semipermeable membrane was implanted in the medial prefrontal cortex. The dialysis probe was perfused at a rate of 1 microl x min(-1) with an artificial cerebrospinal fluid solution. The rats were randomly allocated to two groups: ketamine (group K, n=7) and pentobarbital (group P, n=7). Each rat was subsequently given 0 (saline), 1, 10 and 100 mg x kg(-1) ketamine i.p. in group K, and 0 (saline), 0.5, 5 and 50 mg x kg(-1) pentobarbital i.p. in group P. Sixty minutes elapsed between administration. Noradrenaline concentration was measured by HPLC with an electrochemical detector at 20 min intervals. (detection limit: 250 fg x 20 microl(-1), coefficient variation of the assay: 4.9%). The data in the 20-40 min after each dose of ketamine or pentobarbital i.p. were used for the statistical analysis.


RESULTS
Noradrenaline release after 100 mg x kg(-1) ketamine increased by 7.7 +/- 2.0 (SEM) pg x collection(-1) compared with 2.7 +/- 0.7, 3.3 +/- 1.0 and 4.2 +/- 0.8 pg x collection(-1) after saline, 1 and 10 mg x kg(-1) ketamine, respectively (P < 0.05). Noradrenaline release did not change after pentobarbital.


CONCLUSIONS
This study suggests the ketamine and pentobarbital have different effects on noradrenergic neurons in the medial prefrontal cortex. The stimulating effect of ketamine on noradrenaline release from the cortex might contribute to unique clinical features of ketamine anesthesia.
Kubota
T
T
Department of Anesthesiology, University of Hirosaki School of Medicine, Japan.
Anzawa
N
N
Hirota
K
K
Yoshida
H
H
Kushikata
T
T
Matsuki
A
A
D000759:Adjuvants, Anesthesia / Q000494:pharmacology*; D000316:Adrenergic alpha-Agonists / Q000378:metabolism*; D000704:Analysis of Variance; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis / Q000295:instrumentation; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010424:Pentobarbital / Q000494:pharmacology*; D010919:Placebos; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride; D013566:Sympathomimetics / Q000378:metabolism*; D013997:Time Factors
D000759:Adjuvants, Anesthesia; D000316:Adrenergic alpha-Agonists; D000778:Anesthetics, Dissociative; D018691:Excitatory Amino Acid Antagonists; D018757:GABA Modulators; D010919:Placebos; D013566:Sympathomimetics; D012965:Sodium Chloride; D007649:Ketamine; D010424:Pentobarbital; D009638:Norepinephrine