Gabapentin-induced drug-seeking-like behavior: a potential role for the dopaminergic system

Abstract

Drugs of abuse represent a growing public health crisis. Accumulating evidence indicates that gabapentin (GBP), a prescription drug, is prone to misuse, abuse, withdrawal, and dependence. Commonly, drugs of abuse modulate the dopaminergic system to induce addiction. In this study, we used the conditioned place preference (CPP) model to investigate the involvement of the dopamine 1 (D1) receptor on the reward and reinforcement behavior of GBP. Under a CPP paradigm, male BALB/c mice were intraperitoneally injected either saline or 100, 200, or 300 mg/kg of GBP and confined to the injection-paired chamber for 30 min. In the pre-conditioning phase, mice were conditioned for 3 days, and baseline data were collected. In the conditioning phase, mice were given once-daily alternating injections of either GBP or saline for 8 days and subsequently assessed in a post-conditioning test. Injections of 300 mg/kg of GBP significantly increased the time spent in the drug-paired chamber compared to the saline-paired chamber. However, lower doses of GBP (100 and 200 mg/kg) showed no effect. Pre-treatment with SKF-83566, a D1 receptor antagonist, attenuated GBP-induced CPP. Thus, for the first time, we show that GBP can induce CPP through a dopaminergic-dependent mechanism.

Figure 1

Time spent in conditioning chambers during phases of pre-test and post-test in the groups of the experiment 1: the control (A), GBP 100 (B), GBP 200 (C), and GBP 300 (D) group. No significant changes in time spent were found in chambers during all tested phases in the control, GBP 100 and GBP 200 groups. In GBP 300 group, a significant increase in time spent in GBP-paired chamber as compared to the Saline-paired chamber was found. *p < 0.05. Values shown as means ± S.E.M. N = 7–9/group.

Figure 2

Time spent in conditioning chambers during phases of pre-test and post-test in the groups of the experiment 2: the saline-saline (A), SKF-S (B), S-GBP (C), and SKF-GBP (D) group. No significant changes in time spent were found in chambers during all tested phases in the Saline-Saline and SKF-S groups. In the S-GBP group, a significant increase in time spent in the GBP-paired chamber as compared to the saline-paired chamber was found. SKF pretreatment blocked the GBP-induced increase in time spent. **p < 0.01. Values shown as means ± S.E.M. N = 6–8/group.

Figure 3

Experimental schedule of the CPP.