Persistent sensitisation to the locomotor activating effects of MDMA following MDMA self-administration in rats

Schenk, Susan; Bradbury, Sarah

doi:10.1016/j.pbb.2015.03.001

Cited by 13 publications

(17 citation statements)

References 36 publications

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“…Repeated exposure to experimenter-administered MDMA increased MDMA-stimulated DA release (Kalivas et al, 1998) but MDMA-stimulated DA was not increased following self-administration (Reveron et al, 2010a). Repeated exposure to self-administered MDMA increased MDMA-produced vertical activity (rearing) (Schenk & Bradbury, 2015), a behavioral response that has been attribute to higher tissue levels of DA and lower tissue levels of serotonin (Thiel et al, 1999).…”

Section: Effec Ts Of Repe Ated Mdma On Neurotr Ans Miss Ionmentioning

confidence: 97%

Methylenedioxymethamphetamine (MDMA): Serotonergic and dopaminergic mechanisms related to its use and misuse

Schenk

Highgate

2021

Journal of Neurochemistry

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Methylenedioxymethamphetamine (MDMA) is an amphetamine analogue that preferentially stimulates the release of serotonin (5HT) and results in relatively small increases in synaptic dopamine (DA). The ratio of drug-stimulated increases in synaptic DA, relative to 5HT, predicts the abuse liability; drugs with higher DA:5HT ratios are more likely to be abused. Nonetheless, MDMA is a drug that is misused. Clinical and preclinical studies have suggested that repeated MDMA exposure produces neuroadaptive responses in both 5HT and DA neurotransmission that might explain the development and maintenance of MDMA self-administration in some laboratory animals and the development of a substance use disorder in some humans. In this paper, we describe the research that has demonstrated an inhibitory effect of 5HT on the acquisition of MDMA self-administration and the critical role of DA in the maintenance of MDMA self-administration in laboratory animals. We then describe the circuitry and 5HT receptors that are positioned to modulate DA activity and review the limited research on the effects of MDMA exposure on these receptor mechanisms.

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Section: Effec Ts Of Repe Ated Mdma On Neurotr Ans Miss Ionmentioning

confidence: 97%

Methylenedioxymethamphetamine (MDMA): Serotonergic and dopaminergic mechanisms related to its use and misuse

Schenk

Highgate

2021

Journal of Neurochemistry

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“…MDMA, like other psychostimulant drugs of abuse, increased DA preferentially in the shell of the nucleus accumbens in rats (Cadoni et al, 2005) and this neurochemical effect became sensitized following repeated exposure (Kalivas et al, 1998). Acute exposure to MDMA produced hyperactivity that also became sensitized following repeated exposure (Bradbury et al, 2012, Schenk and Bradbury, 2015, Ball et al, 2009 even in 5-HT transporter knock-out rats (Lizarraga et al, 2014). The locomotor activating effects of MDMA have been shown to be dependent upon A C C E P T E D M A N U S C R I P T…”

Section: Introductionmentioning

confidence: 99%

Serotonin antagonists fail to alter MDMA self-administration in rats

Schenk

Foote

Aronsen

et al. 2016

Pharmacology Biochemistry and Behavior

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“…Longer infusions times and shorter / lack of time out scheduling may also have contributed to higher rates of MDMA self-administration in 13 these studies (De La Garza et al, 2007). Nonetheless, a number of recent studies have reported reliable MDMA self-administration (Aarde, Miller, Creehan, Vandewater, & Taffe, 2015;Ball & Slane, 2012Ball et al, 2015;Ball, Walsh, & Rebec, 2007;Bradbury et al, 2013;Colussi-Mas, Wise, Howard, & Schenk, 2010;Do & Schenk, 2013;Feduccia, Kongovi, & Duvauchelle, 2010;Gould et al, 2011;Kivell, Day, Bosch, Schenk, & Miller, 2010;Oakly, Brox, Schenk, & Ellenbroek, 2013;Reveron, Maier, & Duvauchelle, 2010;Schenk & Bradbury, 2015;Schenk et al, 2007;Z. Wang & Woolverton, 2007).…”

Section: Mdma Self-administrationmentioning

confidence: 97%

“…Locomotor activity was enhanced following repeated experimenter- (Bradbury et al, 2012;Colussi-Mas & Schenk, 2008;Kalivas et al, 1998;Spanos & Yamamoto, 1989) and selfadministered MDMA (Schenk & Bradbury, 2015). Locomotor activity in the centre of the activity chamber was specifically sensitised (Bradbury et al, 2012;Colussi-Mas & Schenk, 2008;Ludwig et al, 2008;McCreary et al, 1999).…”

Section: Acute Behavioural Effects Of Mdmamentioning

confidence: 99%

The role of dopamine D₂ receptor mechanisms in the development of MDMA sensitisation

Wetering¹

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<p>Rationale. ±3, 4-methelynedioxymethamphetamine (MDMA) is the primary psychoactive ingredient of the increasingly popular recreational street drug, ecstasy. As with other drugs of abuse, repeated intermitted exposure to MDMA can lead to an increase in the subsequent behavioural effects of the drug. This phenomenon, termed behavioural sensitisation, has been attributed to sensitisation of central DAergic mechanisms considered to underlie several aspects of addiction. Objectives. The purpose of the present research was to investigate the role of DA D₂ receptor mechanisms in the development of MDMA sensitisation and the acquisition of MDMA self-administration in rats. Methods. Rats received daily i.p. injections of the selective D₂ antagonist, eticlopride (0.0, 0.05, 0.3 mg/kg), prior to injections of MDMA (0.0, 10.0 mg/kg) for five days. Two days following the final pre-treatment session, the locomotor activating effects of MDMA (5 mg/kg, i.p.) were determined. Another group of rats were surgically implanted with i.v. jugular catheters before undergoing the same pre-treatment regimen. Two days following the final pre-treatment session, these rats were subsequently tested for acquisition of MDMA self-administration. The locomotor activating effects of MDMA (5 mg/kg i.p.) were determined two days following the last self-administration session. Results. Pre-treatment with MDMA enhanced the locomotor activating effects of MDMA and facilitated the acquisition of MDMA self-administration, as evidenced by an increased likelihood to meet an acquisition criterion. Co-administration of eticlopride during pre-treatment completely blocked the development of sensitisation to MDMA-produced hyperactivity but failed to significantly attenuate the facilitation of MDMA self-administration. Interestingly, pre-treatment with eticlopride alone also facilitated the acquisition of self-administration. MDMA self-administration failed to alter MDMA-produced locomotor hyperactivity. Conclusions. These findings suggest that repeated activation of DA D₂ receptors is required for the development of sensitisation to MDMA-produced hyperactivity but not for the development of sensitisation to MDMA-produced reinforcement. D₂ receptor mechanisms evidently play some role, however, because repeated exposure to eticlopride also facilitated MDMA self-administration. It is suggested that both sensitised DAergic mechanisms and desensitised 5-HTergic mechanisms contribute to the acquisition of MDMA self-administration.</p>

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Persistent sensitisation to the locomotor activating effects of MDMA following MDMA self-administration in rats

Cited by 13 publications

References 36 publications

Methylenedioxymethamphetamine (MDMA): Serotonergic and dopaminergic mechanisms related to its use and misuse

Methylenedioxymethamphetamine (MDMA): Serotonergic and dopaminergic mechanisms related to its use and misuse

Serotonin antagonists fail to alter MDMA self-administration in rats

The role of dopamine D₂ receptor mechanisms in the development of MDMA sensitisation

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