The Influence of Cryogenic Brain Injury on the Pharmacodynamics of Pentobarbital Evidence for a Serotonergic Mechanism
| Autor: | Naaznin Samanani, David P. Archer, Timothy Tang, Richard E. Priddy, Mary Anne Sabourin |
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| Rok vydání: | 1991 |
| Předmět: |
Male
Serotonin Pentobarbital medicine.medical_specialty Serotonergic Lesion Pharmacokinetics Internal medicine Freezing medicine Animals Infusions Intravenous business.industry Fenclonine Rats Inbred Strains Rats Anesthesiology and Pain Medicine Clamp Endocrinology Brain Injuries Anesthesia Pharmacodynamics Serotonin Antagonists medicine.symptom business medicine.drug |
| Zdroj: | Anesthesiology. 75:634-639 |
| ISSN: | 0003-3022 |
| Popis: | To study of the influence of brain injury on the pharmacodynamics of pentobarbital, the authors examined the effect of a focal cortical freezing lesion in rats on the brain concentration of pentobarbital associated with lack of response to tail clamp. The freezing lesion was made with a probe (-50 degrees C) applied through a craniotomy to the intact dura over the left parietal cortex. Three days after injury the rats were anesthetized with a continuous intravenous infusion of pentobarbital until they first did not respond to tail clamp stimulation. The brains were then removed for determination of pentobarbital by high-performance liquid chromatography. The brain pentobarbital concentration required to prevent response to tail clamp (EC50) was reduced from 209 +/- 39 nmol/g (mean +/- standard deviation) in rats without brain injury to 149 +/- 28 nmol/g in the injured animals (P = 0.005). The cortical serotonin (5-HT) concentration was increased from 1904 +/- 358 pmol/g in uninjured rats to 2513 +/- 598 pmol/g (P less than 0.01) in injured animals ipsilateral to the lesion. Pretreatment of the rats with p-chlorophenylalanine (PCPA, 200 mg/kg by intraperitoneal injection) to inhibit 5-HT synthesis abolished both the increase in 5-HT concentration associated with the injury (left cortex, 708 +/- 389 pmol/g; right cortex, 911 +/- 979 pmol/g) and the effect of the lesion on EC50 (uninjured, EC50 = 186 +/- 24 nmol/g; injured, EC50 = 179 +/- 47 nmol/g). Prevention of the decrease in EC50 by inhibition of 5-HT synthesis provides support for a functional role for 5-HT in the influence of cold injury on the pharmacodynamics of pentobarbital. |
| Databáze: | OpenAIRE |
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