GR 127935 blocks the locomotor and antidepressant-like effects of RU 24969 and the action of antidepressants in the mouse tail suspension test

doi:10.1016/0091-3057(95)02047-0

Pharmacology Biochemistry and Behavior

Volume 53, Issue 3, March 1996, Pages 535-539

https://doi.org/10.1016/0091-3057(95)02047-0 Get rights and content

Abstract

The 5-HT_{$1A B$} agonist RU 24969 induces hyperactivity in rodents and also shows antidepressant-like effects in some animal models of depression. We have examined the effects of selective antagonists at 5-HT_1A and 5-HT_{$1B D$} receptors (WAY 100135 and GR 127935, respectively) on both the hyperlocomotor and anti-immobility effects of RU 24969. While a high dose of WAY 100135 (10 mg/kg) had no effect in either paradigm, GR 127935 attenuated the behavioural effects of RU 24969 in both. WAY 100135 was also without effect on the antidepressant effect of paroxetine, while GR 127935 blocked the effects of paroxetine (1 mg/kg) and imipramine (10 mg/kg). Furthermore, while coadministration of paroxetine or imipramine enhanced the effects of RU 24969 in the mouse tail suspension test, imipramine had no effect on the locomotor activating effects of the 5-HT_1B agonist, suggesting different neural substrates may underly the effects in the different tests. These studies indicate a role for the 5-HT_{$1B D$} receptor in the mediation of the effects of antidepressant treatment.

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Cited by (68)

Serotonin 5-HT<inf>1A</inf> and 5-HT<inf>1B</inf> receptors co-mediate the RU 24969-induced locomotor activity of male and female preweanling rats
2020, Pharmacology Biochemistry and Behavior
Citation Excerpt :
Although RU 24969 has a high affinity for both 5-HT1A and 5-HT1B receptors (Hoyer, 1991), studies using selective 5-HT antagonists alternately report that the RU 24969-induced locomotor activity of adult rats and mice is mediated exclusively by the 5-HT1A receptor (Aronsen et al., 2014; Kalkman, 1995), the 5-HT1B receptor (Chaouloff et al., 1999; Cheetham and Heal, 1993; Shanahan et al., 2009), or both (O'Neill and Parameswaran, 1997). It is interesting that studies examining this question have almost exclusively used the 5-HT1B/1D receptor antagonist GR 127935, while the role of 5-HT1A receptors has been assessed using WAY 100135, WAY 100635, and SDZ 216-525 (Aronsen et al., 2014; Chaouloff et al., 1999; Cheetham and Heal, 1993; Kalkman, 1995; O'Neill and Parameswaran, 1997; O'Neill et al., 1996; Shanahan et al., 2009). Although RU 24969 stimulates locomotor activity and/or patterned limb movements by as early as postnatal day (PD) 1 (Jackson and Kitchen, 1989; Pranzatelli, 1992), it is not known whether the 5-HT1A or 5-HT1B receptor subtype mediates RU 24969's actions during early ontogenetic periods.
The serotonin (5-HT) _1A/1B agonist RU 24969 robustly increases the locomotor activity of adult male rats and mice; however, studies using selective antagonists alternately report that 5-HT_1A, 5-HT_1B, or both receptor types mediate RU 24969's locomotor activating effects. The purpose of the present study was to extend these past findings by administering a selective 5-HT₁ agonist and/or antagonists to male and female preweanling rats. This age group was tested because younger rats often exhibit psychopharmacological responses that are quantitatively or qualitatively different from adult rats. In a series of experiments, male and female preweanling rats were pretreated with vehicle, the 5-HT_1A antagonist WAY 100635 (0.5, 1, 5, or 10 mg/kg), or the 5-HT_1B antagonists NAS-181 (5 or 10 mg/kg) or SB 216641 (5 or 10 mg/kg) 30 min before assessment of locomotor activity. Rats were injected with saline or RU 24969 immediately prior to testing. Results showed that RU 24969 (0.625, 1.25, 2.5, or 5 mg/kg) significantly increased the locomotor activity of both male and female preweanling rats (no sex differences were apparent). Antagonism of either the 5-HT_1A or the 5-HT_1B receptor was sufficient to significantly reduce the locomotor activity of RU 24969-treated preweanling rats. Unexpectedly, NAS-181 did not act as a silent receptor antagonist, as both doses of NAS-181 significantly increased the locomotor activity of saline-treated preweanling rats. In sum, the present results show that both the 5-HT_1A and 5-HT_1B receptor systems mediate locomotion during the late preweanling period, and this mediation does not vary according to sex.
Antidepressant-like effect of the hydroethanolic leaf extract of Alchornea cordifolia (Schumach. & Thonn.) Mull. Arg. (Euphorbiaceae) in mice: Involvement of monoaminergic system
2014, Journal of Ethnopharmacology
The leaf of Alchornea cordifolia (Euphorbiaceae) is used in traditional African medicine in the treatment of various neurological and psychiatric disorders including depression. Previous studies have shown its potent antidepressant-like effect in the forced swimming test (FST). Hence, this study sought to investigate the involvement of monoaminergic systems in the antidepressant-like effect elicited by hydroethanolic leaf extract of Alchornea cordifolia (HeAC) in the FST.
HeAC (25–400 mg/kg, p.o.) was administered 1 h before the FST. To investigate the contribution of monoaminergic systems to antidepressant-like effect, receptors antagonists were injected 15 min before oral administration of HeAC (200 mg/kg) to mice and 1 h thereafter, subjected to FST.
HeAC (200 and 400 mg/kg, p.o.) produced dose dependent and significant (P<0.001) antidepressant-like effect, in the FST, without accompanying changes in spontaneous locomotor activities in the open-field test. The anti-immobility effect of HeAC (200 mg/kg) in the FST was prevented by pretreatment of mice with SCH 23390 (0.05 mg/kg, s.c., a dopamine D₁ receptor antagonist), sulpiride (50 mg/kg, i.p., a dopamine D₂ receptor antagonist), prazosin (1 mg/kg, i.p., an α₁-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α₂-adrenoceptor antagonist), and GR 127993 (5-HT_1B receptor antagonist). Similarly, 3 days intraperitoneal injection of p-chlorophenylalanine (pCPA, 150 mg/kg, i.p., an inhibitor of serotonin synthesis) prevented the antidepressant-like effect elicited by HeAC. The combination of subeffective doses of imipramine (5 mg/kg, p.o.) or fluoxetine (5 mg/kg, p.o.), with HeAC (25 mg/kg, p.o., subeffective dose) produced a synergistic antidepressant-like effect in the FST.
The hydroethanolic extract of Alchornea cordifolia possesses antidepressant-like effect mediated through interaction with dopamine (D₁ and D₂), noradrenergic (α₁ and α₂ adrenoceptors), and serotonergic (5HT_1B receptors) systems. Also, the potentiation of the anti-immobility effect of conventional antidepressants (fluoxetine and imipramine) by Alchornea cordifolia suggest potential therapeutic effect in depression.
A proposal for refining the forced swim test in Swiss mice
2013, Progress in Neuro-Psychopharmacology and Biological Psychiatry
The forced swim test (FST) is a preclinical test to the screening of antidepressants based on rats or mice behaviours, which is also sensitive to stimulants of motor activity. This work standardised and validated a method to register the active and passive behaviours of Swiss mice during the FST in order to strength the specificity of the test. Adult male Swiss mice were subjected to the FST for 6 min without any treatment or after intraperitoneal injection of saline (0.1 ml/10 g), antidepressants (imipramine, desipramine, or fluoxetine, 30 mg/kg) or stimulants (caffeine, 30 mg/kg or apomorphine, 10 mg/kg). The latency, frequency and duration of behaviours (immobility, swimming, and climbing) were scored and summarised in bins of 6, 4, 2 or 1 min. Parameters were first analysed using Principal Components Analysis generating components putatively related to antidepressant (first and second) or to stimulant effects (third). Antidepressants and stimulants affected similarly the parameters grouped into all components. Effects of stimulants on climbing were better distinguished of antidepressants when analysed during the last 4 min of the FST. Surprisingly, the effects of antidepressants on immobility were better distinguished from saline when parameters were scored in the first 2 min. The method proposed here is able to distinguish antidepressants from stimulants of motor activity using Swiss mice in the FST. This refinement should reduce the number of mice used in preclinical evaluation of antidepressants.
Direct and indirect 5-HT receptor agonists produce gender-specific effects on locomotor and vertical activities in C57 BL/6J mice
2009, Pharmacology Biochemistry and Behavior
It is well established that the dopamine (DA) and serotonin (5-HT) systems have extensive and complex interactions. However, the effects of specific 5-HT receptor agonists on traditionally DA-related behaviors remain unclear. Our goal in these studies was to characterize the effects of 5-HT receptor agonists on measures of locomotor activity and vertical rearing. The SSRIs fluoxetine and citalopram produced significant decreases in locomotor activity and vertical rearing at the highest doses used with females significantly more sensitive to citalopram. The 5-HT_1A agonist 8-OH-DPAT and the 5-HT_2C agonist MK 212 significantly decreased activity in both male and female mice, with females more sensitive to 8-OH-DPAT. In contrast, the 5-HT_1B agonist RU 24969 and the 5-HT_2A agonist DOI both increased activity, with DOI exhibiting differential effects with regard to sex. Finally, the 5-HT₃ agonist SR 57227 produced significant locomotor increases only in female mice at the lowest dose. The results of these experiments define locomotor profiles of several 5-HT agonists in male and female C57BL/6J mice, providing a foundation for further explorations of 5-HT receptor effects on activity.
The selective 5-HT<inf>6</inf> receptor antagonist SB-399885 enhances anti-immobility action of antidepressants in rats
2008, European Journal of Pharmacology
The aim of the present study was to investigate the effect of antidepressant drugs (characterized by a different mechanism of action), administered jointly with the selective 5-HT₆ receptor antagonist N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)benzenesulfonamide (SB-399885), in the forced swim test in rats. All the compounds under study were given intraperitoneally in doses which did not shorten the immobility time of rats. Co-administration of SB-399885 (3 mg/kg) and imipramine (20 mg/kg), desipramine (20 mg/kg), bupropion (5 mg/kg) or moclobemide (20 mg/kg), produced significant anti-immobility action, whereas SB-399885 (3 mg/kg) given jointly with citalopram (20 mg/kg) did not affect immobility time. None of the compounds studied, given alone or jointly, increased the general activity of rats measured in the open field test. The obtained results indicate that the blockade of 5-HT₆ receptors may facilitate the anti-immobility effect of imipramine, desipramine, bupropion or moclobemide in the forced swim test.
The antidepressant effects of curcumin in the forced swimming test involve 5-HT<inf>1</inf> and 5-HT<inf>2</inf> receptors
2008, European Journal of Pharmacology
Curcuma longa is a main constituent of many traditional Chinese medicines, such as Xiaoyao-san, used to manage mental disorders effectively. Curcumin is a major active component of C. longa and its antidepressant-like effect has been previously demonstrated in the forced swimming test. The purpose of this study was to explore the possible contribution of serotonin (5-HT) receptors in the behavioral effects induced by curcumin in this animal model of depression. 5-HT was depleted by the tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA, 100 mg/kg, i.p.) prior to the administration of curcumin, and the consequent results showed that PCPA blocked the anti-immobility effect of curcumin in forced swimming test, suggesting the involvement of the serotonergic system. Moreover, pre-treatment of pindolol (10 mg/kg, i.p., a β-adrenoceptors blocker/5-HT_1A/1B receptor antagonist), 4-(2′-methoxy-phenyl)-1-[2′-(n-2″-pyridinyl)-p-iodobenzamino-]ethyl-piperazine (p-MPPI, 1 mg/kg, s.c., a selective 5-HT_1A receptor antagonist), or 1-(2-(1-pyrrolyl)-phenoxy)-3-isopropylamino-2-propanol (isamoltane, 2.5 mg/kg, i.p., a 5-HT_1B receptor antagonist) was found to prevent the effect of curcumin (10 mg/kg) in forced swimming test. On the other hand, a sub-effective dose of curcumin (2.5 mg/kg, p.o.) produced a synergistic effect when given jointly with (+)-8-hydroxy-2-(di-n-propylamino)tetralin, (8-OH-DPAT, 1 mg/kg, i.p., a 5-HT_1A receptor agonist), anpirtoline (0.25 mg/kg, i.p., a 5-HT_1B receptor agonist) or ritanserin (4 mg/kg, i.p., a 5-HT_2A/2C receptor antagonist), but not with ketanserin (5 mg/kg, i.p., a 5-HT_2A/2C receptor antagonist with higher affinity to 5-HT_2A receptor) or R(-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 1 mg/kg, i.p., a 5-HT_2A receptor agonist). Taken together, these results indicate that the antidepressant-like effect of curcumin in the forced swimming test is related to serotonergic system and may be mediated by, at least in part, an interaction with 5-HT_1A/1B and 5-HT_2C receptors.

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ArticleGR 127935 blocks the locomotor and antidepressant-like effects of RU 24969 and the action of antidepressants in the mouse tail suspension test

Abstract

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Article
GR 127935 blocks the locomotor and antidepressant-like effects of RU 24969 and the action of antidepressants in the mouse tail suspension test