title: MDMA ('Ecstasy'), oxytocin and vasopressin modulate social preference in rats: A role for handling and oxytocin receptors.
abstract: In laboratory rats, peripheral administration of the neuropeptides oxytocin (OT) and vasopressin (AVP) induces similar prosocial effects (i.e. increased adjacent lying) to the party drug 3,4-methylenedioxymethamphetamine (MDMA), which are sensitive to vasopressin V1Areceptor (V1AR) antagonism. Here, we employed a social preference paradigm to further compare the prosocial effects of OT, AVP and MDMA. We also investigated the possible involvement of the V1AR and oxytocin receptor (OTR) in rodent social preference. The social preference paradigm measures investigation times towards an empty wire cage (presented for 4min) followed by an identical cage containing a novel rat (also presented for 4min). Social preference is defined as greater investigation time towards the inhabited cage than the empty cage. Results indicated that well-handled rats exhibited no social preference at baseline, while intraperitoneally injected MDMA (5mg/kg), OT (0.5mg/kg) and AVP (0.005mg/kg) increased social preference. However, this effect was primarily due to reduced investigation of the empty cage. In contrast, rats that received minimal prior handling displayed a social preference at baseline, while MDMA (5mg/kg), OT (0.5mg/kg) and AVP (0.005mg/kg) reduced investigation times towards both the empty and inhabited cages. Lower doses of MDMA, OT and AVP were ineffective. The OTR antagonist Compound 25 (C25, 5mg/kg), but not the V1AR antagonist SR49059 (1mg/kg), reduced the baseline social preference seen in minimally-handled rats and prevented the social preference induced by OT and AVP (but not MDMA) in well-handled rats. Overall, these results further confirm prosocial actions of MDMA, OT and AVP, which are dependent on handling history. These findings also indicate that social preference is sensitive to OTR rather than V1AR modulation.
authors.affiliation: School of Psychology, Brennan MacCallum Building, University of Sydney, NSW 2006, Australia.
authors.forename: Linnet
authors.initials: L
authors.lastname: Ramos
authors.affiliation: School of Psychology, Brennan MacCallum Building, University of Sydney, NSW 2006, Australia.
authors.forename: Callum
authors.initials: C
authors.lastname: Hicks
authors.affiliation: School of Psychology, Brennan MacCallum Building, University of Sydney, NSW 2006, Australia.
authors.forename: Alex
authors.initials: A
authors.lastname: Caminer
authors.affiliation: School of Psychology, Brennan MacCallum Building, University of Sydney, NSW 2006, Australia.
authors.forename: Kalliu
authors.initials: K
authors.lastname: Couto
authors.affiliation: School of Chemistry, University of Sydney, NSW 2006, Australia.
authors.forename: Rajeshwar
authors.initials: R
authors.lastname: Narlawar
authors.affiliation: School of Chemistry, University of Sydney, NSW 2006, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
authors.affiliation: School of Psychology, Brennan MacCallum Building, University of Sydney, NSW 2006, Australia. Electronic address: iain.mcgregor@sydney.edu.au.
authors.forename: Iain S
authors.initials: IS
authors.lastname: McGregor
mesh_terms: D000822:Animal Husbandry; D000818:Animals; D007211:Indoles / Q000494:pharmacology; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D010121:Oxytocin / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D018045:Receptors, Oxytocin / Q000502:physiology*; D017483:Receptors, Vasopressin / Q000502:physiology; D012919:Social Behavior; D014667:Vasopressins / Q000494:pharmacology*
chemical_list: D007211:Indoles; D011759:Pyrrolidines; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D014667:Vasopressins; D010121:Oxytocin; C082134:relcovaptan; D018817:N-Methyl-3,4-methylenedioxyamphetamine
keywords: Compound 25; Handling; MDMA; Oxytocin; SR49059; Social preference; Vasopressin