1. Clonidine Inhibition of Norepinephrine Release from Normal and Morphine-Tolerant Guinea Pig Cortical Slices
- Author
-
C. Tomasini, Clementina Bianchi, Lorenzo Beani, and R. Guidorzi
- Subjects
Male ,medicine.medical_specialty ,alpha ,Guinea Pigs ,Stimulation ,Opioid ,In Vitro Techniques ,Biochemistry ,Clonidine ,NO ,Dioxanes ,Guinea pig ,Norepinephrine ,Cellular and Molecular Neuroscience ,Idazoxan ,Reference Values ,Internal medicine ,Receptors ,medicine ,Animals ,Adrenergic alpha-Antagonists ,Cerebral Cortex ,Morphine ,Chemistry ,Drug Tolerance ,Electric Stimulation ,Female ,Receptors, Adrenergic, alpha ,Receptors, Opioid ,Endocrinology ,Adrenergic ,Catecholamine ,Alpha-2 adrenergic receptor ,medicine.drug - Abstract
Endogenous norepinephrine (NE) release in cerebral cortex slices taken from normal and morphine-tolerant guinea pigs was measured by HPLC. In normal slices, a linear relationship was found between electrically evoked NE release and the log of the frequency of stimulation in the range of 1-20 Hz. The efficiency of the alpha 2-mediated autofeedback was tested by adding the alpha 2-agonist clonidine and the alpha 2 agonist idazoxan. NE release was dose-dependently reduced by clonidine (1 nmol/L-1 mumol/L) and increased by idazoxan (10-100 nmol/L). The inhibition by clonidine was significantly greater at 1 Hz than at 3 Hz, whereas the absolute increase in NE release induced by idazoxan was greater at 3 Hz than at 1 Hz. Morphine at 1 mumol/L (a concentration per se ineffective) shifted to the left the clonidine concentrations able to inhibit NE release at 3 and 1 Hz (1-10 nmol/L), but at both frequencies, the opiate reduced the maximal inhibition induced by clonidine at 1 mumol/L. In slices taken from morphine-tolerant guinea pigs (in the presence of morphine at 1 mumol/L), clonidine (1 nmol/L-1 mumol/L) was ineffective at the stimulation rate of 3 Hz, but it was more active than in normal slices at 1 Hz. Such a response pattern suggests a reduced availability of alpha 2 receptors and an increase in their sensitivity to clonidine. However, chronic morphine treatment did not influence the physiological autoinhibition because the increase in NE release elicited by idazoxan (10-100 nmol/L) at 1 and 3 Hz was the same in normal and in "morphine-tolerant" slices.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1992