Effects of the κ-opioid receptor on the inhibition of 100 Hz electroacupuncture on cocaine-induced conditioned place preference

Abstract

The administration of 100 Hz electroacupuncture has been demonstrated to suppress cocaine-induced conditioned place preference (CPP) in rats, and there is evidence that the κ-opioid receptor may have a role in cocaine addiction. The present study sought to explore the mechanisms underlying the inhibitory effects of 100 Hz electroacupuncture on cocaine-induced CPP in rats. A rat model of cocaine-induced CPP was used in the present study to investigate the following: i) Naloxone treatment (5 and 10 mg/kg) following 100 Hz electroacupuncture-mediated inhibition on cocaine-induced CPP, revealing that a high dose (10 mg/kg) of naloxone blocked the inhibitory effects of 100 Hz electroacupuncture on cocaine-induced CPP; ii) nor-binaltorphimine (nor-BNI) on 100 Hz electroacupuncture-mediated inhibition on cocaine-induced CPP, which indicated that administration of 10 µg/5 µl and 0.3 µg/1 µl nor-BNI intracerebroventricularly and via the nucleus accumbens, respectively, reversed the inhibitory effects of 100 Hz electroacupuncture on cocaine-induced CPP, and that injection of nor-BNI in different brain areas of rats blocks the inhibitory effects of electroacupuncture on cocaine-induced CPP; and iv) 100 Hz electroacupuncture on the mRNA expression levels of the κ-opioid receptor in the rat nucleus accumbens and amygdala, which established that mRNA expression levels of κ-opioid receptor in the nucleus accumbens were increased with 100 Hz electroacupuncture plus cocaine-induced CPP. Overall, the results of the present study indicated that 100 Hz electroacupuncture was able to suppress cocaine-induced CPP via the κ-opioid receptor in the nucleus accumbens.

Keywords: cocaine; conditioned place preference; dopamine pathway; electroacupuncture; nor-binaltorphimine; κ-opioid receptor.

Figure 1.

CPP values in rats exposed to different doses of cocaine. Rats were administered 5 or 10 mg/kg cocaine or physiological saline followed by CPP training. n=12 in each group. ***P<0.001, vs. natural preference values. CPP, conditioned place preference.

Figure 2.

Inhibitory effects of 100 Hz electroacupuncture on cocaine-induced CPP. 100 Hz electroacupuncture was administered 24 h prior to the CPP testing. n=12 in each group. ^#P<0.05 and ^##P<0.01 vs. the control group. CPP, conditioned place preference.

Figure 3.

Effect of naloxone on 100 Hz electroacupuncture-mediated inhibition of cocaine-induced CPP. In the naloxone groups, naloxone was injected 24 h after the final conditioning trial. CPP was again tested 24 h after naloxone treatment. In the naloxone + electroacupuncture group, 100 Hz electroacupuncture was delivered 24 h after the final conditioning trial, and naloxone was injected 20 min prior to the electroacupuncture was delivered, while CPP was tested 24 h after the electroacupuncture treatment. n=12 in each group. *P<0.05 and **P<0.01 vs. saline alone. CPP, conditioned place preference.

Figure 4.

Effect of nor-BNI on cocaine-induced CPP. After receiving 10 mg/kg cocaine CPP training, rats were administered 1, 3 or 10 µg/5 µl nor-BNI or physiological saline via the lateral ventricle. n=12 in each group. P>0.05, nor-BNI (all concentrations) vs. saline and control. CPP, conditioned place preference. nor-BNI, nor-binaltorphimine.

Figure 5.

Effect of nor-BNI on 100 Hz electroacupuncture-mediated inhibition of cocaine-induced CPP. Rats received 10 mg/kg cocaine CPP training, then were then given 1, 3 or 10 µg/5 µl nor-BNI or physiological saline via the lateral ventricle. 100 Hz electroacupuncture was conducted 15 min later. n=10 in each group. **P<0.01 vs. physiological saline group; ^#P<0.05 vs. simple restraint group. CPP, conditioned place preference nor-BNI, nor-binaltorphimine.

Figure 6.

Administration of nor-BNI in the NAc reverses 100 Hz electroacupuncture-mediated inhibition of cocaine-induced CPP. Following 10 mg/kg cocaine CPP training, rats were administered 0.03, 0.1 or 0.3 µg/1 µl nor-BNI or physiological saline to the bilateral NAc 15 min prior to 100 Hz electroacupuncture. *P<0.05 vs. simple restraint group. CPP, conditioned place preference. nor-BNI, nor-binaltorphimine; NAc, nucleus accumbens.

Figure 7.

Effect of nor-BNI administration to the ventral tegmental area on 100 Hz electroacupuncture-mediated inhibition of cocaine-induced CPP. Following the administration of 10 mg/kg cocaine CPP training, rats were administered 0.03, 0.1 or 0.3 µg/1 µl nor-BNI or physiological saline in the ventral tegmental area for 15 min prior to 100 Hz electroacupuncture. *P<0.05 vs. simple restraint group. CPP, conditioned place preference; nor-BNI, nor-binaltorphimine.

Figure 8.

Effect of nor-binaltorphimine administration in the amygdala on 100 Hz electroacupuncture-mediated inhibition of cocaine-induced CPP. Received 10 mg/kg cocaine CPP training, rats were given 0.1, 0.3, or 1 µg/1 µl nor-binaltorphimine or physiological saline in the bilateral amygdala central nucleus or bilateral basolateral amygdaloid nucleus 15 min prior to 100 Hz electroacupuncture. *P<0.05 vs. simple restraint group. CPP, conditioned place preference; nor-BNI, nor-binaltorphimine.

Figure 9.

Electroacupuncture (100 Hz) significantly increases the mRNA expression levels of κ-opioid receptor in the nucleus accumbens of rats with cocaine-induced CPP. After receiving 10 mg/kg cocaine CPP training, rats were administered 0.1, 0.3 or 1 µg/1 µl nor-BNI or physiological saline in the bilateral amygdala central nucleus or bilateral basolateral amygdaloid nucleus 15 min prior to 100 Hz electroacupuncture. *P<0.05 vs. cocaine group. CPP, conditioned place preference; nor-BNI, nor-binaltorphimine.

Figure 10.

Effect of 100 Hz electroacupuncture on mRNA expression of κ-opioid receptor in different regions of the amygdala in rats with cocaine-induced CPP. Rats received 10 mg/kg cocaine conditioned place preference training, then the electroacupuncture treatment group rats received 100 Hz electroacupuncture stimulation. Rats from each group were decapitated 2 days later and the amygdala was collected for reverse transcription-polymerase chain reaction to measure the mRNA expression of κ-opioid receptor.