ISSN:
1432-1912
Keywords:
Alpha2-adrenoceptors
;
3H-clonidine binding
;
Tricyclic antidepressants
;
Electroconvulsive shock therapy
;
Pargyline
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Two experimental approaches were used to study the effect of chronic antidepressant treatments on the functioning of central alpha2-adrenoceptors. In one, the effect of antidepressant treatment on the ability of a low dose of clonidine (25 μg/kg) to lower rat brain 3-methoxy-4-hydroxyphenylethyleneglycol sulphate (MHPG-SO4) levels was studied. In the other, potential treatment-induced alterations in rat frontal cortex 3H-clonidine binding were determined. The same cortical tissue was also studied in parallel for 3H-dihydroalprenolol binding. Of the tricyclics imipramine, amitriptyline and nortriptyline, only chronic imipramine (10 mg/kg b.i.d. for 14 days) attenuated the clonidine-induced reduction in brain MHPG-SO4 levels. Repeated electroconvulsive shock therapy (100 mA for 1 s once daily for 10 days), but not chronically administered pargyline, also antagonized the neurochemical response to clonidine. The following long-term antidepressant treatments were investigated for their effect on rat frontal cortex 3H-clonidine and 3H-dihydroalprenolol binding: desipramine, imipramine, nortriptyline, amitriptyline, mianserin, iprindole, nisoxetine, pargyline and electroconvulsive shock therapy. Only chronic pargyline (25 mg/kg once daily for 14 days) altered cortical 3H-clonidine binding. Scatchard analysis revealed that the drug-induced decrease was due to a reduction in the number of recognition sites with no change in affinity. With the exceptions of mianserin and nisoxetine, all other seven forms of antidepressant treatment decreased cortical 3H-dihydroprenolol binding, Scatchard analysis revealing a diminution in the number of recognition sites. The results of this, and previous studies, indicate that under the dosage regimens employed only some forms of long-term antidepressant treatments induce a down-regulation in the functioning of rat brain presynaptic alpha2-adrenoceptors, as assessed by the clonidine-MHPG-SO4 model. No correlation was found between treatment-induced alterations in the characteristics of cortical 3H-clonidine recognition sites and the effect of identical treatment on the clonidine-induced reduction in rat brain MHPG-SO4 levels. To unequivocally assume that drug-induced changes in central 3H-clonidine recognition sites reflect alterations in the functioning of central presynaptic alpha2-adrenoceptors may be open to question.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00506306
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