The effect of 5‐HT_1A receptor agonists on locomotor activity in the guinea‐pig

Abstract

1 The present study examined the effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), flesinoxan, ipsapirone and buspirone, all agonists at the 5-HTIA 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-' 8-OH-DPAT was blocked by the selective 5-HTA antagonist (S)-UH-301 (3.0 and 10.0mg kg-'), but not by (-)-alprenolol (15.0mg kg-'). Ipsapirone (30.0mgkg-') and raclopride (3.0mgkg-') antagonized 8-OH-DPAT-induced locomotor activity but only to a small extent. The 5-HT reuptake inhibitor, zimelidine (10.0 mg kg-') had no effect.4 The effect of the 5-HTIA 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. 5These results support the suggestion that 5-HTIA 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-HTIA agonists also suggests that the degree to which the drugs increase locomotor activity is related to their agonist efficacy at the postsynaptic 5-HTIA receptor.

Hypophagic and dipsogenic effect of the 5‐HT1A receptor agonist 8‐OH‐DPAT in broiler chickens

“…The present findings show that 8-OH-DPAT agonist produces responses in broiler chickens, in the same way as that observed in layer strains (Saadoun and Cabrera, 2002). These results were also consistent with observations made in rats after administrations not only of 8-OH-DPAT, but also with gespirone and buspirone (Gilbert and Dourish, 1987;Fletcher and Davis, 1990;Ebenezer, 1993;Evenden, 1994). Also, the effect of 8-OH-DPAT was investigated in pigs and the results showed the agonist 8-OH-DPAT increased feeding in satiated pigs, while producing a reduction in food intake in refed animals.…”

“…These effects were reported in studies using rats and pigs (Hutson et al., 1988;Voigt et al., 2000). Similar responses were obtained for other 5‐HT 1A agonists including Ipsapirone, buspirone and gepirone (Gilbert and Dourish, 1987; Fletcher and Davis, 1990;Ebenezer, 1992, 1993; Evenden, 1994).…”

The pharmacology of impulsive behaviour in rats IV: the effects of selective serotonergic agents on a paced fixed consecutive number schedule

“…However, there are marked species di¤erences in the e¤ects of acute treatment with 8-OH-DPAT (e.g. Siniscalchi et al 1990;Bill et al 1991;Evenden 1994). In addition, many of the e¤ects of 5-HT 1A agonists show tolerance or sensitisation after repeated administration (Larsson et al 1990, Evenden 1992, which may be relevant to the clinical situation.…”

Effects of 8-hydroxy-2-(di- n -propylamino)tetralin (8-OH-DPAT) on performance on two operant timing schedules

“…In naive rats tested in unfamiliar surroundings, the predominant effect is suppression of locomotion (Tricklebank et al 1984). However, when animals are tested in familiar surroundings, 8-OH-DPAT increases locomotion (Evenden and Ängeby-Möller 1990), an effect that is thought to reflect the low baseline level of activity produced in familiar environments (Evenden 1994). General locomotor behaviour was not measured in these experiments.…”