Discriminative stimulus effects of 3,4-methylenedioxypyrovalerone (MDPV) and structurally related synthetic cathinones.
Alkaloids
/ chemistry
Amphetamines
/ pharmacology
Animals
Behavior, Animal
/ drug effects
Benzodioxoles
/ chemistry
Biogenic Monoamines
/ metabolism
Central Nervous System Stimulants
/ chemistry
Cocaine
/ analogs & derivatives
Discrimination Learning
Dopamine Uptake Inhibitors
/ chemistry
Dose-Response Relationship, Drug
Illicit Drugs
Male
Neurotransmitter Transport Proteins
/ metabolism
Norepinephrine
/ antagonists & inhibitors
Pyrrolidines
/ chemistry
Rats
Rats, Sprague-Dawley
Synthetic Drugs
/ chemistry
Synthetic Cathinone
Journal
Behavioural pharmacology
ISSN: 1473-5849
Titre abrégé: Behav Pharmacol
Pays: England
ID NLM: 9013016
Informations de publication
Date de publication:
01 08 2021
01 08 2021
Historique:
pubmed:
16
2
2021
medline:
22
1
2022
entrez:
15
2
2021
Statut:
ppublish
Résumé
The 3,4-methylenedioxypyrovalerone (MDPV), and other structurally related synthetic cathinones, are popular alternatives to prototypical illicit psychostimulants, such as cocaine and methamphetamine. These drugs are often referred to as 'bath salts' and function either as cocaine-like inhibitors of monoamine uptake, or amphetamine-like substrates for dopamine, norepinephrine and serotonin transporters. These studies used male Sprague-Dawley rats trained to discriminate MDPV from saline to evaluate the substitution profiles of structurally related synthetic cathinones, cocaine, and other direct-acting dopamine and noradrenergic receptor agonists in order to characterize the relative contributions of dopamine, norepinephrine and serotonin to the discriminative stimulus effects of MDPV. As expected, each of the cathinones and cocaine dose-dependently increased MDPV-appropriate responding, with a rank-order potency that was positively correlated with their potency to inhibit dopamine and norepinephrine, but not serotonin, a relationship that is consistent with the rank order to maintain self-administration. The dopamine D2/3 receptor-preferring agonist quinpirole produced a modest increase in MDPV-appropriate responding, whereas the dopamine D1/5 receptor agonist, SKF 82958, nonselective dopamine receptor agonist, apomorphine, as well as the α-1, and α-2 adrenergic receptor agonists, phenylephrine and clonidine, respectively, failed to increase MDPV-appropriate responding at doses smaller than those that suppressed responding altogether. Although these studies do not support a role for serotonergic or adrenergic systems in mediating/modulating the discriminative stimulus effects of MDPV, convergent evidence is provided to suggest that the discriminative stimulus effects of MDPV are primarily mediated by its capacity to inhibit dopamine uptake, and the subsequent activation of dopamine D2 or D3 receptors.
Identifiants
pubmed: 33587482
doi: 10.1097/FBP.0000000000000624
pii: 00008877-202108000-00001
pmc: PMC8266731
mid: NIHMS1660907
doi:
Substances chimiques
Alkaloids
0
Amphetamines
0
Benzodioxoles
0
Biogenic Monoamines
0
Central Nervous System Stimulants
0
Dopamine Uptake Inhibitors
0
Illicit Drugs
0
Neurotransmitter Transport Proteins
0
Pyrrolidines
0
Synthetic Drugs
0
cathinone
540EI4406J
Cocaine
I5Y540LHVR
Norepinephrine
X4W3ENH1CV
Synthetic Cathinone
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
357-367Subventions
Organisme : NIDA NIH HHS
ID : R01 DA039146
Pays : United States
Organisme : NIDA NIH HHS
ID : R36 DA050955
Pays : United States
Organisme : NINDS NIH HHS
ID : T32 NS082145
Pays : United States
Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Références
Baladi MG, France CP. (2010). Eating high-fat chow increases the sensitivity of rats to quinpirole-induced discriminative stimulus effects and yawning. Behav Pharmacol. 21:615–620.
Baladi MG, Newman AH, France CP. (2014). Feeding condition and the relative contribution of different dopamine receptor subtypes to the discriminative stimulus effects of cocaine in rats. Psychopharmacology (Berl). 231:581–591.
Baumann MH, Ayestas MA Jr, Partilla JS, Sink JR, Shulgin AT, Daley PF, et al. (2012). The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Neuropsychopharmacology. 37:1192–1203.
Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, et al. (2013). Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive ‘bath salts’ products. Neuropsychopharmacology. 38:552–562.
Berquist MD 2nd, Baker LE. (2017). Characterization of the discriminative stimulus effects of 3,4-methylenedioxypyrovalerone in male Sprague-Dawley rats. Behav Pharmacol. 28:394–400.
Berquist MD 2nd, Thompson NA, Baker LE. (2017). Evaluation of training dose in male Sprague-Dawley rats trained to discriminate 4-methylmethcathinone. Psychopharmacology (Berl). 234:3271–3278.
Collins GT, Abbott M, Galindo K, Rush EL, Rice KC, France CP. (2016). Discriminative stimulus effects of binary drug mixtures: studies with cocaine, MDPV, and caffeine. J Pharmacol Exp Ther. 359:1–10.
Collins GT, Jackson JA, Koek W, France CP. (2014). Effects of dopamine D(2)-like receptor agonists in mice trained to discriminate cocaine from saline: influence of feeding condition. Eur J Pharmacol. 729:123–131.
Cunningham KA, Callahan PM. (1991). Monoamine reuptake inhibitors enhance the discriminative state induced by cocaine in the rat. Psychopharmacology (Berl). 104:177–180.
DeLarge AF, Erwin LL, Winsauer PJ. (2017). Atypical binding at dopamine and serotonin transporters contribute to the discriminative stimulus effects of mephedrone. Neuropharmacology. 119:62–75.
Desai RI, Barber DJ, Terry P. (1999). Asymmetric generalization between the discriminative stimulus effects of nicotine and cocaine. Behav Pharmacol. 10:647–656.
Desai RI, Barber DJ, Terry P. (2003). Dopaminergic and cholinergic involvement in the discriminative stimulus effects of nicotine and cocaine in rats. Psychopharmacology (Berl). 167:335–343.
Desai RI, Bergman J. (2010). Drug discrimination in methamphetamine-trained rats: effects of cholinergic nicotinic compounds. J Pharmacol Exp Ther. 335:807–816.
Drug Enforcement Administration, Department of Justice. (2011) Schedules of controlled substances: temporary placement of three synthetic cathinones in Schedule I. Final Order. Fed Regist. 76:65371–65375.
Drug Enforcement Administration, Department of Justice. (2014) Schedules of controlled substances: temporary placement of 10 synthetic cathinones into Schedule I. Final order. Fed Regist. 79:12938–12943.
Eshleman AJ, Wolfrum KM, Hatfield MG, Johnson RA, Murphy KV, Janowsky A. (2013). Substituted methcathinones differ in transporter and receptor interactions. Biochem Pharmacol. 85:1803–1815.
Eshleman AJ, Wolfrum KM, Reed JF, Kim SO, Swanson T, Johnson RA, Janowsky A. (2017). Structure-activity relationships of substituted cathinones, with transporter binding, uptake, and release. J Pharmacol Exp Ther. 360:33–47.
Fantegrossi WE, Gannon BM, Zimmerman SM, Rice KC. (2013). In vivo effects of abused ‘bath salt’ constituent 3,4-methylenedioxypyrovalerone (MDPV) in mice: drug discrimination, thermoregulation, and locomotor activity. Neuropsychopharmacology. 38:563–573.
Ferré S. (1997) Adenosine-dopamine interactions in the ventral striatum. Implications for the treatment of schizophrenia. Psychopharmacology (Berl). 133:107–120.
Gannon BM, Baumann MH, Walther D, Jimenez-Morigosa C, Sulima A, Rice KC, Collins GT. (2018a). 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 BM, Galindo KI, Mesmin MP, Sulima A, Rice KC, Collins GT. (2018b) 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 BM, Williamson A, Suzuki M, Rice KC, Fantegrossi WE. (2016). Stereoselective effects of abused “bath salt” constituent 3,4-methylenedioxypyrovalerone in mice: drug discrimination, locomotor activity, and thermoregulation. J Pharmacol Exp Ther. 356:615–623.
Garrett BE, Holtzman SG. (1994). D1 and D2 dopamine receptor antagonists block caffeine-induced stimulation of locomotor activity in rats. Pharmacol Biochem Behav. 47:89–94.
Garrett BE, Holtzman SG. (1996). Comparison of the effects of prototypical behavioral stimulants on locomotor activity and rotational behavior in rats. Pharmacol Biochem Behav. 54:469–477.
Gatch MB, Dolan SB, Forster MJ. (2015a). Comparative behavioral pharmacology of three pyrrolidine-containing synthetic cathinone derivatives. J Pharmacol Exp Ther. 354:103–110.
Gatch MB, Dolan SB, Forster MJ. (2017). Locomotor activity and discriminative stimulus effects of a novel series of synthetic cathinone analogs in mice and rats. Psychopharmacology (Berl). 234:1237–1245.
Gatch MB, Dolan SB, Forster MJ. (2019). Locomotor activity and discriminative stimulus effects of five novel synthetic cathinone analogs in mice and rats. Drug Alcohol Depend. 199:50–58.
Gatch MB, Dolan SB, Forster MJ. (2020). Methylenedioxymethamphetamine-like discriminative stimulus effects of seven cathinones in rats. Behav Pharmacol. 31:378–384.
Gatch MB, Forster MJ. (2020). Methylenedioxymethamphetamine-like discriminative stimulus effects of pyrrolidinyl cathinones in rats. J Psychopharmacol. 34:778–785.
Gatch MB, Rutledge MA, Forster MJ. (2015b). Discriminative and locomotor effects of five synthetic cathinones in rats and mice. Psychopharmacology (Berl). 232:1197–1205.
Gatch MB, Taylor CM, Forster MJ. (2013). Locomotor stimulant and discriminative stimulus effects of ‘bath salt’ cathinones. Behav Pharmacol. 24:437–447.
Harvey EL, Baker LE. (2016). Differential effects of 3,4-methylenedioxypyrovalerone (MDPV) and 4-methylmethcathinone (mephedrone) in rats trained to discriminate MDMA or a d-amphetamine + MDMA mixture. Psychopharmacology (Berl). 233:673–680.
Harvey EL, Burroughs RL, Baker LE. (2017). Effects of D1 and D2 receptor antagonists on the discriminative stimulus effects of methylendioxypyrovalerone and mephedrone in male Sprague-Dawley rats trained to discriminate D-amphetamine. Behav Pharmacol. 28:586–589.
Johnson PS, Johnson MW. (2014). Investigation of “bath salts” use patterns within an online sample of users in the United States. J Psychoactive Drugs. 46:369–378.
Kleven MS, Koek W. (1997). Discriminative stimulus properties of cocaine: enhancement by beta-adrenergic receptor antagonists. Psychopharmacology (Berl). 131:307–312.
Kyle PB, Iverson RB, Gajagowni RG, Spencer L. (2011). Illicit bath salts: not for bathing. J Miss State Med Assoc. 52:375–377.
Mumford GK, Holtzman SG. (1991). Qualitative differences in the discriminative stimulus effects of low and high doses of caffeine in the rat. J Pharmacol Exp Ther. 258:857–865.
Munzar P, Nosál R, Goldberg SR. (1998). Potentiation of the discriminative-stimulus effects of methamphetamine by the histamine H3 receptor antagonist thioperamide in rats. Eur J Pharmacol. 363:93–101.
Munzar P, Goldberg SR. (1999). Noradrenergic modulation of the discriminative-stimulus effects of methamphetamine in rats. Psychopharmacology (Berl). 143:293–301.
Munzar P, Goldberg SR. (2000). Dopaminergic involvement in the discriminative-stimulus effects of methamphetamine in rats. Psychopharmacology (Berl). 148:209–216.
Murray BL, Murphy CM, Beuhler MC. (2012). Death following recreational use of designer drug “bath salts” containing 3,4-Methylenedioxypyrovalerone (MDPV). J Med Toxicol. 8:69–75.
National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. (2011) Guide for the Care and Use of Laboratory Animals. 8th edn. Washington (DC): National Academies Press (US)
Powell KR, Koppelman LF, Holtzman SG. (1999). Differential involvement of dopamine in mediating the discriminative stimulus effects of low and high doses of caffeine in rats. Behav Pharmacol. 10:707–716.
Quinton MS, Gerak LR, Moerschbaecher JM, Winsauer PJ. (2006). Effects of pregnanolone in rats discriminating cocaine. Pharmacol Biochem Behav. 85:385–392.
Risca HI, Baker LE. (2019). Contribution of monoaminergic mechanisms to the discriminative stimulus effects of 3,4-methylenedioxypyrovalerone (MDPV) in Sprague-Dawley rats. Psychopharmacology (Berl). 236:963–971.
Schechter MD. (1997). Discriminative characteristics of high and low cocaine administration: effect of other psychostimulants. Pharmacol Biochem Behav. 56:457–463.
Simmler LD, Buser TA, Donzelli M, Schramm Y, Dieu LH, Huwyler J, et al. (2013). Pharmacological characterization of designer cathinones in vitro . Br J Pharmacol. 168:458–470.
Simmler LD, Rickli A, Hoener MC, Liechti ME. (2014). Monoamine transporter and receptor interaction profiles of a new series of designer cathinones. Neuropharmacology. 79:152–160.
Solinas M, Ferré S, You ZB, Karcz-Kubicha M, Popoli P, Goldberg SR. (2002). Caffeine induces dopamine and glutamate release in the shell of the nucleus accumbens. J Neurosci. 22:6321–6324.
Spealman RD. (1995). Noradrenergic involvement in the discriminative stimulus effects of cocaine in squirrel monkeys. J Pharmacol Exp Ther. 275:53–62.
Spiller HA, Ryan ML, Weston RG, Jansen J. (2011). Clinical experience with and analytical confirmation of “bath salts” and “legal highs” (synthetic cathinones) in the United States. Clin Toxicol (Phila). 49:499–505.
Wood DM, Lal H, Yaden S, Emmett-Oglesby MW. (1985). One-way generalization of clonidine to the discriminative stimulus produced by cocaine. Pharmacol Biochem Behav. 23:529–533.