Comparative study of alpha2-adrenoceptors in Fischer 344 and Lewis rats. Evidence for clonidine-induced place aversion.

Full Abstract

Fischer 344 (F344) and Lewis rat strains have been shown to exhibit different vulnerability to development or maintenance of opioid seeking behaviours probably due to differences in the endogenous opioid system. Since opioid and alpha(2)-adrenergic mechanisms closely interact in nociception and substance abuse, strain differences may be expected to affect alpha(2)-adrenoceptor-mediated events. The sensitivity of these two strains to alpha(2)-adrenoceptor-mediated antinociception has been reported to be markedly different. In this work we have further studied the function of alpha(2)-adrenoceptors in F344 and Lewis rats by means of several in vivo and in vitro procedures. Comparative studies of [(3)H]RX821002 and [(35)S]GTPgammaS binding revealed that alpha(2)-adrenoceptors could be slightly more responsive to agonist stimulation in the brain cortex of F344 rats, which is in agreement with previous antinociception studies. However, these differences were modest, not observed in the spinal cord and did not translate into functional differences concerning the effects of clonidine on vas deferens contractility and body temperature. Conditioning experiments showed that a moderate dose of clonidine, which is relevant in antinociceptive and opioid antiwithdrawal studies, induces a robust place aversion which is also equivalent in F344 and Lewis rats. This finding underlies the consistency of the effect and its independency of genetic differences between both rat strains. It seems therefore that the pharmacological properties of alpha(2)-adrenoceptors are similar in F344 and Lewis rats, and thus the previously reported differences in clonidine-induced antinociception could be attributed to other factors such as dissimilar endogenous function of specific noradrenergic pathways.

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Author information

Author/s: Herradón, Gonzalo (G); Morales, Lidia (L); Gramage, Esther (E); Alguacil, Luis F (LF);

Affiliation: Lab. Pharmacology and Toxicology, University San Pablo CEU, Urb. Montepríncipe, 28668 Boadilla del Monte, Madrid, Spain. herradon(-atsign-)ceu.es

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Journal: Life sciences (Life Sci), published in England. (Language: eng)

Reference: 2008-Jun; vol 82 (issue 23-24) : pp 1186-90

Dates: Created 2008/05/26; Completed 2008/07/21;

PMID: 18479715, status: MEDLINE (last retrieval date: 11/6/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adrenergic alpha-Agonists - pharmacology
Animals
Behavior, Animal - drug effects
Binding Sites
Brain - drug effects; metabolism
Clonidine - pharmacology
Conditioning, Operant - drug effects
Electric Stimulation
Male

Male
Protein Binding
Rats
Rats, Inbred F344
Rats, Inbred Lew
Receptors, Adrenergic, alpha-2 - agonists; physiology
Species Specificity
Spinal Cord - drug effects; metabolism
Vas Deferens - drug effects; metabolism

Associated Chemicals: Adrenergic alpha-Agonists (0) ; Receptors, Adrenergic, alpha-2 (0) ; Clonidine (4205-90-7)

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