TL neuro

September 1, 2015

MDPV and Methylone self-administration in rats

Filed under: Cathinones, Methylone — mtaffe @ 1:19 pm

A new paper from the Designer Drugs Research Unit within the NIDA IRP compares the self-administration of MDPV and methylone in rats. Methylone (3,4-methylenedioxymethcathinone) appears to have replaced MDMA in the NFLIS forensic laboratory database 2013-2014. This is only the third group to publish self-administration data with methylone so this is a very welcome tie-breaker. Watterson and colleagues (2012) reported fairly robust self-administration of methylone in male Sprague-Dawley rats and we reported marginal to weak self-administration in both female and male Wistar rats.

Schindler CW1, Thorndike EB, Goldberg SR, Lehner KR, Cozzi NV, Brandt SD, Baumann MH. Reinforcing and neurochemical effects of the “bath salts” constituents 3,4-methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) in male rats. Psychopharmacology (Berl). 2015 Aug 29. [Epub ahead of print] [ PubMed ]

Schindler15-Fig1IVSAIn this new study the authors trained male Sprague-Dawley rats to self-administer MDPV (0.03 mg/kg/infusion) or methylone (0.3 mg/kg/infusion) in two hour sessions during the dark (active) cycle. This figure to the right depicts nose-poke responses for the drug-associated (active) and non-associated (inactive) holes. Sessions indicated by A indicate Acquisition and E1-E6 indicate extinction sessions in which no drug resulted from a nose-poke response. Shaded symbols indicate when active and inactive responding was significantly different. The comparison makes it clear that while basic self-administration criteria were established for both drugs (active and inactive responding differed) the MDPV group made more responses than the methylone-trained group. They also exhibited a clear patter of self-administration from the second day of training compared with the seventh session for methylone. A followup study (Fig 2 of the paper) trained a group on a slightly higher 0.5 mg/kg/inf methylone dose (identical to the one we used and the highest, most effective dose used in the Watterson et al (2012) study). This group was given 17 acquisition sessions and the trajectory of behavior matched that of the 0.3 mg/kg group.

Schindler15-DoseResponse After acquisition, and before the extinction sessions reported in the first figure, the authors conducted a dose-substitution procedure in which the MDPV and 0.3 mg/kg/inf methylone [I didn’t mention the cocaine-trained group in the above discussion, but they were included in the study.] animals were given varying doses of drug in each infusion on different days. Each dose was provided on three consecutive days and the intakes on days 2-3 are reported here. As you can see, the methylone trained animals were insensitive to dose-substitution, particularly in comparison with MDPV (or cocaine) trained rats. This is very similar to our finding, particularly if you consider that the Schindler paper didn’t use a dose of methylone higher than 0.5 mg/kg/infusion in their procedure. In Vandewater et al (2015) and in Creehan et al (2015) the methylone-trained male and female rats really only expressed differences in intake between 0.125 and 2.5 mg/kg/inf doses. The functions were pretty linear (and descending, like the cocaine one shown above) but they were very shallow.

The take-away message is pretty similar to our studies and discordant with the findings of Watterson, et al 2012, 2014. Methylone supports low levels of self-administration in rats, but to a much lower extent than does MDPV in a direct comparison here. A similar indirect comparison of our studies (Vandewater et al 2015; Creehan et al 2015 vs Aarde et al, 2013, Aarde et al, 2015) comes to the same conclusion.


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