RU 24969-produced adipsia and hyperlocomotion: Differential role of 5HT1A and 5HT1B receptor mechanisms

Aronsen, Dane; Webster, Jeremy; Schenk, Susan

doi:10.1016/j.pbb.2014.05.008

Cited by 14 publications

(13 citation statements)

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“…Our results suggest that as higher doses of RU24969 induce greater hyperlocomotion, digging behavior is eliminated through response competition. This finding is consistent with recent work demonstrating reduced home cage drinking with increasing doses of RU24969 in rodents (Aronsen et al 2014). It is unclear how the effects of RU24969 treatment on splashinduced grooming, but not digging, are independent from locomotor activity.…”

Section: Discussionsupporting

confidence: 91%

Clinically effective OCD treatment prevents 5-HT1B receptor-induced repetitive behavior and striatal activation

Thompson

Katzka

et al. 2015

Psychopharmacology

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Section: Discussionsupporting

confidence: 91%

Clinically effective OCD treatment prevents 5-HT1B receptor-induced repetitive behavior and striatal activation

Thompson

Katzka

et al. 2015

Psychopharmacology

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“…Reinstatement of extinguished drug-taking behavior produced by a priming injection of MDMA was not altered by the 5-HT 1A antagonist, WAY 100635, the 5-HT 1B antagonist, GR 127935 or the 5-HT 2A antagonist, ketanserin. Doses of the antagonists used were pharmacologically effective, attenuated other drug-produced behaviors (Aronsen et al, 2014) and attenuated MDMA-produced hyperactivity (present results). Some of the antagonists also decreased cocaine-produced drug-seeking (present results).…”

Section: Serotonin and Self-administrationsupporting

confidence: 68%

Serotonin antagonists fail to alter MDMA self-administration in rats

Schenk

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Aronsen

et al. 2016

Pharmacology Biochemistry and Behavior

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“…Tolerance to RU 24969-produced hyperactivity was produced following repeated exposure to the 5-HT 1B/1A receptor agonist (Oberlander, Demassey, Verdu, Van de Velde, & Bardelay, 1987). As outlined in the previous chapter, we have recently shown that RU 24969-produced hyperactivity in rats is due to activation of 5-HT 1A , but not 5-HT 1B , receptors (Aronsen, Webster, & Schenk, 2014), suggesting that behavioural tolerance reflects a down-regulation of this receptor subtype. The effect of RU 24969 pretreatment on 5-HT 1B receptor mechanisms has not been specifically measured, but RU 24969-produced adipsia provides a means of addressing this question (Aronsen et al, 2014).…”

Section: Discussionmentioning

confidence: 78%

“…As outlined in the previous chapter, we have recently shown that RU 24969-produced hyperactivity in rats is due to activation of 5-HT 1A , but not 5-HT 1B , receptors (Aronsen, Webster, & Schenk, 2014), suggesting that behavioural tolerance reflects a down-regulation of this receptor subtype. The effect of RU 24969 pretreatment on 5-HT 1B receptor mechanisms has not been specifically measured, but RU 24969-produced adipsia provides a means of addressing this question (Aronsen et al, 2014). Therefore, in the present study we determined the effect of repeated exposure to RU 24969 on the acquisition of MDMA selfadministration, and on RU 24969-produced adipsia.…”

Section: Discussionmentioning

confidence: 79%

“…RU 24969 (3.0 mg/kg, s.c.), or the saline vehicle (1.0 ml/kg), was administered in the home cage daily at 0900hr and 1600hr, for three consecutive days. This protocol was adapted from that used in earlier studies (Callaway & Geyer, 1992;Oberlander et al, 1987) to utilise a dose of RU 24969 that we have previously shown produces both hyperactivity and adipsia (Aronsen et al, 2014).…”

Section: Ru 24969 Pretreatmentmentioning

confidence: 99%

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The role of 5-HT1A and 5-HT1B receptors in MDMA self-administration

Aronsen¹

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<p>Rationale: 3,4-methylenedioxymethamphetamine (MDMA) is a less efficacious reinforcer than other drugs of abuse. However, following repeated self-administration, responding increases for some animals and efficacy becomes comparable to other drugs of abuse. MDMA-stimulated serotonin (5-HT) release was negatively associated with acquisition of MDMA self-administration, and a neurotoxic 5-HT lesion reduced the latency to acquire self-administration. These findings suggest that MDMA-produced 5-HT release is an important component of self-administration. The receptor mechanisms are not, however, well understood, although it has often been suggested that the mechanism involves 5-HT-mediated inhibition of dopamine. Both 5-HT1A and 5-HT1B receptors are well localised to regulate dopamine release, and both have been implicated in modulating the reinforcing effects of many drugs of abuse. Objectives: The first objective was to establish specific behavioural assays to reflect 5-HT1A and 5-HT1B receptor activation. Then, using the established behavioural assays, the aim was to determine the role of 5-HT1A and 5-HT1B receptors in the acquisition of MDMA self-administration. The impact of substantial MDMA self-administration on 5-HT1A and 5-HT1B receptors was also assessed. Methods: Firstly, dose-effect relationships for the hyperactive response to the 5-HT1A receptor agonist, 8-OH-DPAT (0 – 3.0 mg/kg) and the hyperactive and adipsic response to the 5-HT1B/1A receptor agonist, RU 24969 (0 – 3.0 mg/kg) were determined. Selectivity of these responses was determined by co-administration of the 5-HT1A receptor antagonist, WAY 100635, or the 5-HT1B/1D receptor antagonist, GR 127935. Secondly, a pretreatment regimen of the RU 24969 (2 × 3.0 mg/kg/day, 3 days), which had been suggested to down-regulate 5-HT1B/1A receptors, was administered prior to self-administration testing. The effect of this manipulation on both the acquisition of MDMA self-administration, and the behavioural responses to 5-HT1A and 5-HT1B receptor activation, was measured. A further study measured behavioural responses to 5-HT1A or 5-HT1B receptor agonists prior to self-administration, to determine whether the variability in these responses would predict the variability in the latency to acquisition of MDMA self-administration. Lastly, the effect of substantial MDMA self-administration (350 mg/kg) on dose-response curves for the behavioural effects of 5-HT1A or 5-HT1B receptor activation was assessed. Results: The hyperactive response to the 5-HT1B/1A receptor agonist, RU 24969, was blocked by the 5-HT1A receptor antagonist, WAY 100635, but not the 5-HT1B receptor antagonist, GR127935. Similarly, the hyperactive response to the 5-HT1A receptor agonist, 8-OH-DPAT, was dose-dependently blocked by WAY 100635. GR 127935, but not WAY 100635, blocked the adipsic response to RU 24969. Repeated administration of RU 24969 produced rightward shifts in the dose-response curves for 8-OH-DPAT-produced hyperactivity and RU 24969-produced adipsia, and also greatly facilitated the acquisition of MDMA self-administration. However, there was no correlation between latency to acquire MDMA self-administration and the hyperactive response to 8-OH-DPAT or the adipsic response to RU 24969, and MDMA self-administration failed to alter these behavioural response to activation of 5-HT1A or 5-HT1B receptors. Conclusions: The hyperactive response to 8-OH-DPAT and the adipsic response to RU 24969 reflect activation of 5-HT1A and 5-HT1B receptors, respectively. The variability in acquisition of MDMA self-administration was reduced by a treatment that also down-regulated 5-HT1A and 5-HT1B receptors, however there was no further indication that these receptors play a critical role in the self-administration of MDMA. Instead, it seems likely that other 5-HT receptors have a greater impact on MDMA self-administration.</p>

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RU 24969-produced adipsia and hyperlocomotion: Differential role of 5HT1A and 5HT1B receptor mechanisms

Cited by 14 publications

References 24 publications

Clinically effective OCD treatment prevents 5-HT1B receptor-induced repetitive behavior and striatal activation

Clinically effective OCD treatment prevents 5-HT1B receptor-induced repetitive behavior and striatal activation

Serotonin antagonists fail to alter MDMA self-administration in rats

The role of 5-HT1A and 5-HT1B receptors in MDMA self-administration

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