Cortical [3H]ketanserin binding and 5-HT2A receptor-mediated inositol phosphate production in the spontaneously hypertensive rat and Lewis rat strains.
The spontaneously hypertensive rat (SHR) and Lewis rat strains differ in the elevated plus-maze of anxiety, the former and the latter strain displaying low and high anxiety, respectively. A recent study has shown that serotonin (5-hydroxytryptamine, 5-HT)2A receptor-mediated head shakes, but not [3H]ketanserin binding at these receptors, are less in Lewis rats, compared with SHRs. Herein, we have analysed the hypothesis of a difference in 5-HT2A receptor-effector coupling between these two strains. Confirming our previous results, the Bmax and KD values for the specific [3H]ketanserin binding at cortical 5-HT2A receptors were respectively identical in both strains. The accumulation of total inositol phosphates by the 5-HT2A,2B,2C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 0.01-100 microM) was concentration- and strain (Lewis > SHR)-dependent. Preincubation with 0.01 and 0.1 microM of the 5-HT2A receptor antagonist SR 46349B, respectively, decreased and prevented DOI-elicited inositol phosphate production in both strains. The aforementioned genetic differences in 5-HT2A receptor-mediated head shakes may thus lie at some point distal from the 5-HT2A receptor.
Gauffre
J C
JC
INSERM CJF 94-05, INRA, Institut F. Magendie, Bordeaux, France.
Aguerre
S
S
Mormède
P
P
Chaouloff
F
F
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005464:Fluorobenzenes / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism*; D007650:Ketanserin / Q000493:pharmacokinetics*; D008297:Male; D010636:Phenols / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D011918:Rats, Inbred SHR; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000502:physiology*; D013045:Species Specificity
D000662:Amphetamines; D000959:Antihypertensive Agents; D005464:Fluorobenzenes; D007295:Inositol Phosphates; D010636:Phenols; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; C076033:SR 46349B; C076823:1-(2,5-dimethyl-4-iodophenyl)-2-aminopropane; D007650:Ketanserin