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Comparative Study
. 2016 Sep;27(6):497-505.
doi: 10.1097/FBP.0000000000000237.

Locomotor, discriminative stimulus, and place conditioning effects of MDAI in rodents

Michael B Gatch  1 , Sean B Dolan, Michael J Forster
Affiliations
Comparative Study

Locomotor, discriminative stimulus, and place conditioning effects of MDAI in rodents

Michael B Gatch et al. Behav Pharmacol. 2016 Sep.

Abstract

5,6-Methylenedioxy-2-aminoindane (MDAI) has become a common substitute for (±)-3,4-methylenedioxymethamphetamine (MDMA) in Ecstasy. MDAI is known to produce MDMA-like discriminative stimulus effects, but it is not known whether MDAI has psychostimulant or hallucinogen-like effects. MDAI was tested for locomotor stimulant effects in mice and subsequently for discriminative stimulus effects in rats trained to discriminate cocaine (10 mg/kg, intraperitoneally), methamphetamine (1 mg/kg, intraperitoneally), ±MDMA (1.5 mg/kg, intraperitoneally), or (-)-2,5-dimethoxy-4-methylamphetamine hydrochloride (0.5 mg/kg, intraperitoneally) from saline. The ability of MDAI to produce conditioned place preference was also tested in mice. MDAI (3 to 30 mg/kg) depressed locomotor activity from 10 to 60 min. A rebound stimulant effect was observed at 1 to 3.5 h following 30 mg/kg. Lethality occurred in 8/8 mice following 100 mg/kg MDAI. Similarly, MDMA depressed locomotor activity immediately following the administration of 0.25 mg/kg and stimulant effects were observed 50-70 min following the administration of 0.5 and 1 mg/kg. MDAI fully substituted for the discriminative stimulus effects of MDMA (2.5 mg/kg), (-)-2,5-dimethoxy-4-methylamphetamine hydrochloride (5 mg/kg), and cocaine (7.5 mg/kg), but produced only 73% methamphetamine-appropriate responding at a dose that suppressed responding (7.5 mg/kg). MDAI produced tremors at 10 mg/kg in one methamphetamine-trained rat. MDAI produced conditioned place preference from 0.3 to 10 mg/kg. The effects of MDAI on locomotor activity and drug discrimination were similar to those produced by MDMA, having both psychostimulant-like and hallucinogen-like effects; thus, MDAI may have similar abuse potential as MDMA.

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Figures

Fig 1
Fig 1
Time course of locomotor activity in mice. Data are represented as mean number of ambulation counts for each 10-minute period over 8 hours for each dose of MDMA (left) and MDAI (right). Data are from independent groups of 8 mice per dose. Vehicle (0.9% saline) data were obtained from one group of mice and displayed in each panel to indicate dose-dependent differences of drug-induced motor activity from vehicle-treated mice. The gray bars show the time ranges of maximal depressant and stimulant effects. * indicates doses significantly different from vehicle for the period of 0–30 minutes after injection, as determined by a two-way analysis of variance (p < 0.05).
Fig. 2
Fig. 2
Substitution of MDAI for the discriminative stimulus effects of MDMA, cocaine, methamphetamine, or DOM in rats. The upper panel shows percentage of total responses on the drug-appropriate lever as a function of log dose of MDAI. The lower panel shows rate of responding in responses per second (r/s). Data are from groups of 6 rats. Ctrl indicates average of responding to vehicle (0.9% saline) and drug controls. * indicates response rate different from vehicle control (p < 0.05).
Fig. 3
Fig. 3
Time course of the discriminative stimulus effects of MDAI. Percentage of total responses made on the drug-appropriate lever as a function of time (shown in log increments). The dose of MDAI was the dose that produced peak effects in the dose-effect study without suppressing response rate to the point that rats failed to respond (2.5 mg/kg in MDMA-trained rats, and 5 mg/kg in cocaine-, methamphetamine- and DOM-trained rats. The upper panel shows percentage of total responses on the drug-appropriate lever. The lower panel shows rate of responding in responses per second (r/s). n=6 except where shown. V indicates vehicle values. * indicates rate different (p < 0.05) from vehicle control.
Fig. 4
Fig. 4
Conditioned place preference in mice. Preference scores (time spent on drug-paired floor during pre-test subtracted from time spent on drug-paired floor during post-test) as a function of log dose of MDAI. Data are from independent groups of n=16 mice per dose. * indicates doses significantly different from baseline (p < 0.05).
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References

    1. Bilsky EJ, Hui YZ, Hubbell CL, Reid LD. Methylenedioxymethamphetamine’s capacity to establish place preferences and modify intake of an alcoholic beverage. Pharmacol Biochem Behav. 1990;37:633–8. - PubMed
    1. Callahan PM, Appel JB, Cunningham KA. Dopamine D1 and D2 mediation of the discriminative stimulus properties of d-amphetamine and cocaine. Psychopharmacology (Berl) 1990;103:50–55. - PubMed
    1. Callaway CW, Wing LL, Geyer MA. Serotonin release contributes to the locomotor stimulant effects of 3,4-methylenedioxymethamphetamine in rats. J Pharmacol Exp Ther. 1990;254:456–64. - PubMed
    1. Carroll FI, Blough BE, Abraham P, Mills AC, Holleman JA, Wolckenhauer SA, Decker AM, Landavazo A, McElroy KT, Navarro HA, Gatch MB, Forster MJ. Synthesis and biological evaluation of bupropion analogues as potential pharmacotherapies for cocaine addiction. J Med Chem. 2009;52:6768–81. - PubMed
    1. Casale JF, Hays PA. Characterization of the “Methylenedioxy-2-aminoindans”. Microgram J. 2011;8:43–52.

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