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The effect of 5‐HT 1A receptor agonists on locomotor activity in the guinea‐pig
Author(s) -
Evenden J.L.
Publication year - 1994
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.1476-5381.1994.tb13159.x
Subject(s) - ipsapirone , raclopride , chemistry , buspirone , agonist , 8 oh dpat , pharmacology , medicine , endocrinology , antagonist , 5 ht receptor , partial agonist , serotonin , receptor , biology , biochemistry
1 The present study examined the effects of 8‐hydroxy‐2‐(din‐propylamino)tetralin (8‐OH‐DPAT), flesinoxan, ipsapirone and buspirone, all agonists at the 5‐HT 1A receptor, on the locomotor activity of guinea‐pigs. The effects of these drugs were contrasted with those of the non‐selective 5‐HT agonist, 5‐methoxy‐ N,N ‐dimethyl tryptamine (5‐MeO‐DMT) and the dopamine D 2 antagonist, raclopride. 2 8‐OH‐DPAT, flesinoxan and 5‐MeO‐DMT markedly increased the locomotor activity of naive, unhabituated guinea‐pigs in a dose‐dependent manner. Buspirone also did so, although to a lesser extent and for a shorter time. The doses at which this effect was seen were higher than those normally employed in rats. Ipsapirone and raclopride had no significant effects on locomotor activity. 3 The locomotor activity increasing effect of 1.0 mg kg −1 8‐OH‐DPAT was blocked by the selective 5‐HT 1A antagonist (S)‐UH‐301 (3.0 and 10.0 mg kg −1 ), but not by (−)‐alprenolol (15.0 mg kg −1 ). Ipsapirone (30.0 mg kg −1 ) and raclopride (3.0 mg kg −1 ) antagonized 8‐OH‐DPAT‐induced locomotor activity but only to a small extent. The 5‐HT reuptake inhibitor, zimelidine (10.0 mg kg −1 ) had no effect. 4 The effect of the 5‐HT 1A agonists in the guinea‐pig contrasts with the effects of 8‐OH‐DPAT on the locomotor activity of unhabituated rats and mice tested in the same apparatus, but are similar to the effects of 8‐OH‐DPAT on habituated rats, which show a low baseline of activity. 5 These results support the suggestion that 5‐HT 1A agonists may have an intrinsic activating effect which may be masked by other effects of the drug (e.g. hypothermia, 5‐HT syndrome). The rank ordering of the 5‐HT 1A agonists also suggests that the degree to which the drugs increase locomotor activity is related to their agonist efficacy at the postsynaptic 5‐HT 1A receptor.