Recently, the abuse of synthetic cathinones is increasing
among
young people. α-Pyrrolidinobutiothiophenone (α-PBT), a
synthetic cathinone, is a designer drug that is freely traded online
with no legal restrictions. Moreover, there is currently no scientific
basis for legal regulation. Here, we examined the addictive properties
of α-PBT using a drug discrimination (DD) task. We also investigated
the role of α-PBT in brain stimulation reward (BSR) using an
intracranial self-stimulation (ICSS) paradigm in rats. Initially,
the rats were trained to discriminate between cocaine and saline.
After the discrimination training criteria were met, we determined
the dose–effect curves of cocaine and conducted generalization
tests with α-PBT and α-pyrrolidinopentiothiophenone (α-PVT)
using a cumulative dosing protocol. In a separate set of studies,
we examined the dopaminergic mechanisms underlying the function of
α-PBT as an interoceptive stimulus (17.8 mg/kg) by intraperitoneally
injecting either the dopamine (DA) D1 antagonist SCH23390 (0.06 and
0.12 mg/kg) or the D2 antagonist eticlopride (0.05 and 0.1 mg/kg)
15 min before DD testing. Brain reward function was measured using
an ICSS procedure to examine the effects of α-PBT on ICSS threshold
under the frequency-rate procedure. Our results showed that α-PBT
functioned as a discriminative cue similar to cocaine in rats. More
importantly, SCH23390 abolished the effects of α-PBT as an interoceptive
stimulus in a dose-dependent manner in rats trained to press a lever
to receive cocaine. Similarly, eticlopride dose-dependently attenuated
the effect of α-PBT used as a discriminative cue. Additionally,
cumulative α-PBT administration dose-dependently lowered ICSS
thresholds compared with those in saline-treated rats. Furthermore,
α-PBT-induced potentiation of BSR was abolished by pretreatment
with both SCH23390 and eticlopride. Taken together, our results suggest
that α-PBT can function as a cocaine-like discriminative cue
via the activation of D1 and D2 receptors. α-PBT also appears
to influence BSR by reducing the brain reward threshold via changes
in D1 and D2 receptors. The present study suggests that α-PBT
could have addictive properties through DA D1 and D2 receptors and
thus poses a threat to humans.