Background And Purpose: α-Pyrrolidinobutiothiophenone (α-PBT) is a chemical derivative of cathinone, a structural analogue of amphetamine. Until now, there have been a few previous neurochemical or neurobehavioural studies on the abuse potential of α-PBT.
Experimental Approach: We examined the abuse potential of α-PBT by measuring psychomotor, rewarding, and reinforcing properties and methamphetamine-like discriminative stimulus effects in rodents using locomotor activity, conditioned place preference, self-administration, and drug discrimination studies. To clarify the underlying neuropharmacological mechanisms, we measured dopamine levels and neuronal activation in the dorsal striatum. In addition, we investigated the role of the dopamine D receptor or D receptors in α-PBT-induced hyperlocomotor activity, conditioned place preference, and the methamphetamine-like discriminative stimulus effect of α-PBT in rodents.
Key Results: α-PBT promoted hyperlocomotor activity in mice. α-PBT induced drug-paired place preference in mice and supported self-administration in rats. In a drug discrimination experiment, α-PBT fully substituted for the discriminative stimulus effects of methamphetamine in rats. Furthermore, α-PBT increased dopamine levels and c-Fos expression in the dorsal striatum of mice, which was associated with these behaviours. Finally, pretreatment with the D receptor antagonist SCH23390 or the D receptors antagonist eticlopride significantly attenuated acute or repeated α-PBT-induced hyperlocomotor activity, place preference, and the methamphetamine-like discriminative stimulus effects in rodents.
Conclusions And Implications: These findings suggest that α-PBT has abuse potential at the highest dose tested via enhanced dopaminergic transmission in the dorsal striatum of rodents. The results provide scientific evidence for the legal restrictions of the recreational use of α-PBT.
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http://dx.doi.org/10.1111/bph.16422 | DOI Listing |
J Neurosci
January 2025
Neuroscience and Cognitive Science Program, University of Maryland, College Park, Maryland, 20742.
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Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, CNY 149, 13th St, Charlestown, MA, 02129, USA.
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Department of Psychology, Hebei Normal University, Shijiazhuang, China. Electronic address:
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Departament de Psicobiologia i de Metodologia de les Ciències de la Salut, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, Spain; Centro de Investigación Biomédica En Red en Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Unitat de Neurociència Traslacional, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí (I3PT), Institut de Neurociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain; ICREA, Barcelona, Spain. Electronic address:
Women are known to have twice as much lifetime prevalence of post-traumatic stress disorder (PTSD) as men do. It has been reported that the risk genotype (CC) of a single nucleotide polymorphism (SNP) (rs2267735) in the pituitary adenylate cyclase-activating polypeptide (PACAP-PAC1R) system is associated with PTSD risk and altered fear conditioning and fear extinction in women. Surprisingly, no previous work has studied the effect of this SNP on fear conditioning, extinction, or generalization in non-traumatized/low trauma load women.
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