The effect of 5‐HT1A receptor agonists on locomotor activity in the guinea‐pig

• Published in: British journal of pharmacology Vol. 112; no. 3; pp. 861 - 866
• Main Author: Evenden, J.L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-07-1994; Nature Publishing
• Subjects: 5‐Hydroxytryptamine agonists; 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology; 8‐OH‐DPAT; Animals; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Drug Interactions; Fundamental and applied biological sciences. Psychology; Guinea Pigs; locomotor activity in guinea‐pig; Male; Motor Activity - drug effects; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - pharmacology; Serotonin Uptake Inhibitors - pharmacology; Vertebrates: nervous system and sense organs; Zimeldine - pharmacology; Locomotion; Vertebrata; Agonist; Mammalia; Spontaneous physical activity; Guinea pig; Rodentia; Central nervous system; Mechanism of action; Biological activity; Comparative study; 5-HT1A receptor
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1994.tb13159.x

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‐HT1A 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 D2 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‐HT1A 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‐HT1A 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‐HT1A 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‐HT1A agonists also suggests that the degree to which the drugs increase locomotor activity is related to their agonist efficacy at the postsynaptic 5‐HT1A receptor.