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Behavioural evidence for functional interactions between 5‐HT‐receptor subtypes in rats and mice
Author(s) -
Berendsen Hemmie H.G.,
Broekkamp Chris L.E.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb14138.x
Subject(s) - agonist , hypoactivity , 8 oh dpat , chemistry , 5 ht receptor , endocrinology , medicine , serotonin agonist , 5 ht1a receptor , receptor , serotonin , partial agonist , pharmacology , biology
1 Different 5‐hydroxytryptamine (5‐HT) receptor subtypes mediate different behavioural responses. Compounds acting at more than one 5‐HT receptor exert behavioural effects which may be the result of response competition or a specific interaction between pathways within the CNS. Therefore the mutual interaction between different 5‐HT receptor subtypes was studied. 2 Hypothermia and hypoactivity in mice induced by the 5‐HT 1A ‐agonist 8‐hydroxy‐dipropylaminotetralin (8‐OH‐DPAT) could be attenuated by the preferential 5‐HT 1C ‐agonists MK 212, 1‐(meta‐chlorophenyl)‐piperazine (mCPP) and m‐trifluoromethyl phenyl piperazine (TFMPP), and by the mixed 5‐HT 2/1C ‐agonist 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOI). The mixed 5‐HT 1A/1B ‐agonist CGS 12066B at 10 mg kg −1 potentiated hypothermia and had no effect on hypoactivity. 3 Forepaw treading in rats induced by the 5‐HT 1A ‐agonist 8‐OH‐DPAT was attenuated by the 5‐HT 1C ‐agonists MK 212 and mCPP. The 5‐HT 1C ‐agonist TFMPP had a bimodal effect: at low doses (> 1 mg kg −1 ) it potentiated, and at higher doses (> 2.2 mg kg −1 ) it attenuated forepaw treading. the mixed 5‐HT 2/1C ‐agonist DOI produced 5‐HT 2 ‐related behaviours and potentiated 8‐OH‐DPAT‐induced forepaw treading. This indicates an attenuating effect of 5‐HT 1C ‐receptor activation and a potentiating effect of 5‐HT 2 ‐receptor activation. CGS 12066B had no effect in this respect. 4 Head shakes in rats induced by DOI could be attenuated by 8‐OH‐DPAT, TFMPP, mCPP and MK 212. The ID 50 s were 0.03, 0.7, 0.1 and 2 mg kg −1 , respectively. This suggests that a 5‐HT 2 ‐receptor‐mediated effect may be attenuated by activation of 5‐HT 1A ‐ or 5‐HT 1C ‐receptors. CGS 12066B attenuated the head shake response but only at 10 mg kg −1 . 5 The results suggest that interactions exist between the different 5‐HT receptor subtype‐mediated events. Therefore, care is needed in drawing conclusions from functional measurements when compounds have more or less equal affinities for more than one 5‐HT‐receptor subtype.