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Effects of α-pyrrolidinopentiophenone and 4-methyl-N-ethylcathinone, two synthetic cathinones commonly found in second-generation "bath salts," on intracranial self-stimulation thresholds in rats.
Int J Neuropsychopharmacol. 2014 Oct 31; 18(1)IJ

Abstract

BACKGROUND

Use of synthetic cathinones, which are designer stimulants found in "bath salts," has increased dramatically in recent years. Following governmental bans of methylenedioxypyrovalerone, mephedrone, and methylone, a second generation of synthetic cathinones with unknown abuse liability has emerged as replacements.

METHODS

Using a discrete trials current intensity threshold intracranial self-stimulation procedure, the present study assessed the effects of 2 common second-generation synthetic cathinones, α-pyrrolidinopentiophenone (0.1-5 mg/kg) and 4-methyl-N-ethcathinone (1-100 mg/kg) on brain reward function. Methamphetamine (0.1-3 mg/kg) was also tested for comparison purposes.

RESULTS

Results revealed both α-pyrrolidinopentiophenone and 4-methyl-N-ethcathinone produced significant intracranial self-stimulation threshold reductions similar to that of methamphetamine. α-Pyrrolidinopentiophenone (1 mg/kg) produced a significant maximal reduction in intracranial self-stimulation thresholds (~19%) most similar to maximal reductions produced by methamphetamine (1 mg/kg, ~20%). Maximal reductions in intracranial self-stimulation thresholds produced by 4-methyl-N-ethcathinone were observed at 30 mg/kg (~15%) and were comparable with those observed with methamphetamine and α-pyrrolidinopentiophenone tested at the 0.3-mg/kg dose (~14%). Additional analysis of the ED50 values from log-transformed data revealed the rank order potency of these drugs as methamphetamine ≈ α-pyrrolidinopentiophenone>4-methyl-N-ethcathinone.

CONCLUSIONS

These data suggest that the newer second-generation synthetic cathinones activate the brain reward circuitry and thus may possess a similar degree of abuse potential as prototypical illicit psychostimulants such as methamphetamine as well as the first generation synthetic cathinone methylenedioxypyrovalerone, as previously reported.

Authors+Show Affiliations

Arizona State University, Department of Psychology, Behavioral Neuroscience Area, Tempe, Arizona (Dr Watterson, Mr Burrows, Mr Hernandez, and Dr Olive); Arizona State University Interdisciplinary Graduate Program in Neuroscience, Tempe, Arizona (Dr Olive); Discovery and Analytical Science, Research Triangle Institute International, Research Triangle Park, North Carolina (Drs Moore, Grabenauer, and Marusich). lrwatter@asu.edu.Arizona State University, Department of Psychology, Behavioral Neuroscience Area, Tempe, Arizona (Dr Watterson, Mr Burrows, Mr Hernandez, and Dr Olive); Arizona State University Interdisciplinary Graduate Program in Neuroscience, Tempe, Arizona (Dr Olive); Discovery and Analytical Science, Research Triangle Institute International, Research Triangle Park, North Carolina (Drs Moore, Grabenauer, and Marusich).Arizona State University, Department of Psychology, Behavioral Neuroscience Area, Tempe, Arizona (Dr Watterson, Mr Burrows, Mr Hernandez, and Dr Olive); Arizona State University Interdisciplinary Graduate Program in Neuroscience, Tempe, Arizona (Dr Olive); Discovery and Analytical Science, Research Triangle Institute International, Research Triangle Park, North Carolina (Drs Moore, Grabenauer, and Marusich).Arizona State University, Department of Psychology, Behavioral Neuroscience Area, Tempe, Arizona (Dr Watterson, Mr Burrows, Mr Hernandez, and Dr Olive); Arizona State University Interdisciplinary Graduate Program in Neuroscience, Tempe, Arizona (Dr Olive); Discovery and Analytical Science, Research Triangle Institute International, Research Triangle Park, North Carolina (Drs Moore, Grabenauer, and Marusich).Arizona State University, Department of Psychology, Behavioral Neuroscience Area, Tempe, Arizona (Dr Watterson, Mr Burrows, Mr Hernandez, and Dr Olive); Arizona State University Interdisciplinary Graduate Program in Neuroscience, Tempe, Arizona (Dr Olive); Discovery and Analytical Science, Research Triangle Institute International, Research Triangle Park, North Carolina (Drs Moore, Grabenauer, and Marusich).Arizona State University, Department of Psychology, Behavioral Neuroscience Area, Tempe, Arizona (Dr Watterson, Mr Burrows, Mr Hernandez, and Dr Olive); Arizona State University Interdisciplinary Graduate Program in Neuroscience, Tempe, Arizona (Dr Olive); Discovery and Analytical Science, Research Triangle Institute International, Research Triangle Park, North Carolina (Drs Moore, Grabenauer, and Marusich).Arizona State University, Department of Psychology, Behavioral Neuroscience Area, Tempe, Arizona (Dr Watterson, Mr Burrows, Mr Hernandez, and Dr Olive); Arizona State University Interdisciplinary Graduate Program in Neuroscience, Tempe, Arizona (Dr Olive); Discovery and Analytical Science, Research Triangle Institute International, Research Triangle Park, North Carolina (Drs Moore, Grabenauer, and Marusich).

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25522379

Citation

Watterson, Lucas R., et al. "Effects of Α-pyrrolidinopentiophenone and 4-methyl-N-ethylcathinone, Two Synthetic Cathinones Commonly Found in Second-generation "bath Salts," On Intracranial Self-stimulation Thresholds in Rats." The International Journal of Neuropsychopharmacology, vol. 18, no. 1, 2014.
Watterson LR, Burrows BT, Hernandez RD, et al. Effects of α-pyrrolidinopentiophenone and 4-methyl-N-ethylcathinone, two synthetic cathinones commonly found in second-generation "bath salts," on intracranial self-stimulation thresholds in rats. Int J Neuropsychopharmacol. 2014;18(1).
Watterson, L. R., Burrows, B. T., Hernandez, R. D., Moore, K. N., Grabenauer, M., Marusich, J. A., & Olive, M. F. (2014). Effects of α-pyrrolidinopentiophenone and 4-methyl-N-ethylcathinone, two synthetic cathinones commonly found in second-generation "bath salts," on intracranial self-stimulation thresholds in rats. The International Journal of Neuropsychopharmacology, 18(1). https://doi.org/10.1093/ijnp/pyu014
Watterson LR, et al. Effects of Α-pyrrolidinopentiophenone and 4-methyl-N-ethylcathinone, Two Synthetic Cathinones Commonly Found in Second-generation "bath Salts," On Intracranial Self-stimulation Thresholds in Rats. Int J Neuropsychopharmacol. 2014 Oct 31;18(1) PubMed PMID: 25522379.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of α-pyrrolidinopentiophenone and 4-methyl-N-ethylcathinone, two synthetic cathinones commonly found in second-generation "bath salts," on intracranial self-stimulation thresholds in rats. AU - Watterson,Lucas R, AU - Burrows,Brian T, AU - Hernandez,Raymundo D, AU - Moore,Katherine N, AU - Grabenauer,Megan, AU - Marusich,Julie A, AU - Olive,M Foster, Y1 - 2014/10/31/ PY - 2014/12/19/entrez PY - 2014/12/19/pubmed PY - 2015/10/1/medline KW - ICSS KW - abuse liability KW - bath salts KW - psychostimulants KW - synthetic cathinones JF - The international journal of neuropsychopharmacology JO - Int J Neuropsychopharmacol VL - 18 IS - 1 N2 - BACKGROUND: Use of synthetic cathinones, which are designer stimulants found in "bath salts," has increased dramatically in recent years. Following governmental bans of methylenedioxypyrovalerone, mephedrone, and methylone, a second generation of synthetic cathinones with unknown abuse liability has emerged as replacements. METHODS: Using a discrete trials current intensity threshold intracranial self-stimulation procedure, the present study assessed the effects of 2 common second-generation synthetic cathinones, α-pyrrolidinopentiophenone (0.1-5 mg/kg) and 4-methyl-N-ethcathinone (1-100 mg/kg) on brain reward function. Methamphetamine (0.1-3 mg/kg) was also tested for comparison purposes. RESULTS: Results revealed both α-pyrrolidinopentiophenone and 4-methyl-N-ethcathinone produced significant intracranial self-stimulation threshold reductions similar to that of methamphetamine. α-Pyrrolidinopentiophenone (1 mg/kg) produced a significant maximal reduction in intracranial self-stimulation thresholds (~19%) most similar to maximal reductions produced by methamphetamine (1 mg/kg, ~20%). Maximal reductions in intracranial self-stimulation thresholds produced by 4-methyl-N-ethcathinone were observed at 30 mg/kg (~15%) and were comparable with those observed with methamphetamine and α-pyrrolidinopentiophenone tested at the 0.3-mg/kg dose (~14%). Additional analysis of the ED50 values from log-transformed data revealed the rank order potency of these drugs as methamphetamine ≈ α-pyrrolidinopentiophenone>4-methyl-N-ethcathinone. CONCLUSIONS: These data suggest that the newer second-generation synthetic cathinones activate the brain reward circuitry and thus may possess a similar degree of abuse potential as prototypical illicit psychostimulants such as methamphetamine as well as the first generation synthetic cathinone methylenedioxypyrovalerone, as previously reported. SN - 1469-5111 UR - https://www.unboundmedicine.com/medline/citation/25522379/Effects_of_α_pyrrolidinopentiophenone_and_4_methyl_N_ethylcathinone_two_synthetic_cathinones_commonly_found_in_second_generation_"bath_salts"_on_intracranial_self_stimulation_thresholds_in_rats_ L2 - https://academic.oup.com/ijnp/article-lookup/doi/10.1093/ijnp/pyu014 DB - PRIME DP - Unbound Medicine ER -