The past 5 years have seen a dramatic increase in the abuse of synthetic cathinones (e.g., MDPV and methylone), which are marketed as bath salts, and are widely available for purchase on the internet and in local shops as safe and legal highs. In addition to a high potential for abuse, bath salts also have a high potential fr toxicity, characterized by severe cardiovascular and neuropsychiatric complications. Although the mechanisms that contribute to these high rates of abuse and toxicity are currently unclear, it is important to note that bath salts are most often mixtures of multiple psychoactive drugs, including mixtures of two different synthetic cathinones, or mixtures of a synthetic cathinone and caffeine. This proposal consists of three independent aims focused on comparing the reinforcing effectiveness, relapse-related behaviors, and toxic effects of bath salts mixtures (MDPV + methylone, MDPV + caffeine, and methylone + caffeine) with those of synthetic cathinones alone (MDPV and methylone). This project combines well-established animal models of abuse (self-administration) and toxicity (cardiovascular recordings) with isobolographic analysis to evaluate the highly innovative hypotheses that common bath salts mixtures are (1) more potent and effective reinforcers than synthetic cathinones alone; (2) more effective at strengthening drug-stimuli associations involved in relapse than synthetic cathinones alone; and (3) more potent and effective at producing tachycardia and hypertension as well as other features of the bath salts toxidrome than synthetic cathinones alone. Together, the results of the proposed studies will provide essential information about factors that contribute to the high rates of bath salts abuse and toxicity. This new knowledge will guide development of novel and targeted treatments for the ever-increasing and evolving problem of bath salts abuse.

Public Health Relevance

Designer stimulants (i.e., synthetic cathinones, 'bath salts') are associated with high rates of abuse and toxicity. Importantly, 'bath salts' are most often mixtures of multiple psychoactive drugs (e.g., two different synthetic cathinones, or a synthetic cathinone and caffeine). This project combines well-established animal models of abuse (self-administration) and toxicity (cardiovascular recordings) with isobolographic analysis to determine whether the abuse-related and toxic effects of synthetic cathinones are enhanced when they are administered in combination with other common 'bath salts' constituents. Together, the results of the proposed studies will provide essential information about factors that contribute to the high rates of 'bath salts' abuse and toxicity, ultimately advancing efforts to develop novel and effective treatments for this ever-increasing and evolving drug abuse problem.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA039146-05
Application #
9632790
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Rapaka, Rao
Project Start
2015-04-01
Project End
2020-01-31
Budget Start
2019-02-01
Budget End
2020-01-31
Support Year
5
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Texas Health Science Center
Department
Pharmacology
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
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Gannon, Brenda M; Galindo, Kayla I; Mesmin, Melson P et al. (2018) Relative reinforcing effects of second-generation synthetic cathinones: Acquisition of self-administration and fixed ratio dose-response curves in rats. Neuropharmacology 134:28-35
Gannon, Brenda M; Baumann, Michael H; Walther, Donna et al. (2018) The abuse-related effects of pyrrolidine-containing cathinones are related to their potency and selectivity to inhibit the dopamine transporter. Neuropsychopharmacology 43:2399-2407
Gannon, Brenda M; Sulima, Agnieszka; Rice, Kenner C et al. (2018) Inhibition of Cocaine and 3,4-Methylenedioxypyrovalerone (MDPV) Self-Administration by Lorcaserin Is Mediated by 5-HT2C Receptors in Rats. J Pharmacol Exp Ther 364:359-366
Gannon, Brenda M; Mesmin, Melson P; Sulima, Agnieszka et al. (2018) Behavioral economic analysis of the reinforcing effects of ""bath salts"" mixtures: studies with MDPV, methylone, and caffeine in male Sprague-Dawley rats. Psychopharmacology (Berl) :
Gannon, Brenda M; Rice, Kenner C; Collins, Gregory T (2017) Reinforcing effects of abused 'bath salts' constituents 3,4-methylenedioxypyrovalerone and ?-pyrrolidinopentiophenone and their enantiomers. Behav Pharmacol 28:578-581
Gannon, Brenda M; Galindo, Kayla I; Rice, Kenner C et al. (2017) Individual Differences in the Relative Reinforcing Effects of 3,4-Methylenedioxypyrovalerone under Fixed and Progressive Ratio Schedules of Reinforcement in Rats. J Pharmacol Exp Ther 361:181-189
Collins, Gregory T; Abbott, Megan; Galindo, Kayla et al. (2016) Discriminative Stimulus Effects of Binary Drug Mixtures: Studies with Cocaine, MDPV, and Caffeine. J Pharmacol Exp Ther 359:1-10