Involvement of the dopaminergic system in the reward-related behavior of pregabalin

Abstract

There has been an increase in cases of drug addiction and prescription drug abuse worldwide. Recently, pregabalin abuse has been a focus for many healthcare agencies, as highlighted by epidemiological studies. We previously evaluated the possibility of pregabalin abuse using the conditioned place preference (CPP) paradigm. We observed that a 60 mg/kg dose could induce CPP in mice and that pregabalin-rewarding properties were mediated through glutamate neurotransmission. Notably, the dopaminergic reward circuitry is also known to play a crucial role in medication-seeking behavior. Therefore, this study aimed to explore the possible involvement of dopaminergic receptor-1 in pregabalin-induced CPP. Mice were randomly allocated to receive saline or the dopamine-1 receptor antagonist SKF-83566 (0.03 mg/kg, intraperitoneal). After 30 min, the mice received either saline or pregabalin (60 mg/kg) during the conditioning phase. Among the control groups that received saline or SKF-83566, the time spent in the two conditioning chambers was not significantly altered. However, among the pregabalin-treated group, there was a marked increase in the time spent in the drug-paired chamber compared to the time spent in the vehicle-paired chamber. Notably, blocking dopamine-1 receptors with SKF-83566 completely prevented pregabalin-induced place preference, thus demonstrating the engagement of the dopaminergic system in pregabalin-induced reward-related behavior.

Figure 1

(A) Timeline of the CPP experiment. (B) The four experimental groups.

Figure 2

Time spent in the conditioning chambers during the pre and postconditioning tests in the saline-saline (A) and SKF-saline (B) groups. (A) There were no significant changes in the time spent in chamber 1 and 2 during all tested phases (n = 6). (B) There were no significant changes in the time spent in the saline-paired chamber compared to the SKF-paired chamber during the pre and postconditioning tests (n = 8). Values are reported as means ± standard error of the mean.

Figure 3

Time spent in the conditioning chambers during the pre and postconditioning tests in the saline-pregabalin (A) and SKF-pregabalin (B) groups. (A) The mice spent significantly more time in the pregabalin-paired chamber during the postconditioning test compared to the preconditioning test. Moreover, there was a significant increase in the time spent in the pregabalin-paired chamber during the postconditioning test compared to that spent in the saline-paired chamber (n = 6). Values are reported as means ± standard error of the mean. (B) There was no significant change in the time spent in the conditioning chambers during the pre and postconditioning tests in the SKF-pregabalin group (n = 7). Values are reported as means ± standard error of the mean (**p < 0.01, & p < 0.05 compared to the preconditioning test).