Effects of acupuncture on stress-induced relapse to cocaine-seeking in rats

Abstract

Rationale Cocaine addiction is associated with high rates of relapse, and stress has been identified as a major risk factor. We have previously demonstrated that acupuncture reduces drug self-administration and dopamine release in the nucleus accumbens (NAc), a brain structure implicated in stress-induced reinstatement of drug-seeking behavior. Objective This study was conducted to investigate the effects of acupuncture on footshock-induced reinstatement of cocaine-seeking and the expression of c-Fos and the transcription factor cAMP response element-binding protein (CREB) in the NAc, used as markers of neuronal activation in conditions of stress-induced reinstatement to cocaine. Methods Male Sprague–Dawley rats were trained to self-administer cocaine (1.0 mg/kg) for 14 days, followed by extinction and then footshock stress. Acupuncture was applied at bilateral Shenmen (HT7) points for 1 min after footshock stress. Results and conclusions Acute footshock stress reinstated cocaine-seeking behavior and enhanced c-Fos expression and phosphorylated CREB (pCREB) activation in the NAc shell in cocaine pre-exposed rats. On the other hand, acupuncture at HT7, but not at control point (LI5), markedly reduced reinstatement of cocaine-seeking (86.5 % inhibition vs. control value), c-Fos expression (81.7% inhibition), and pCREB activation (79.3% inhibition) in the NAc shell. These results suggest that acupuncture attenuates stress-induced relapse by regulating neuronal activation in the NAc shell.

Hippocampal cAMP/PKA/CREB is required for neuroprotective effect of acupuncture

“…The effects of acupuncture on WMW tasks and CREB phosphorylation in the presence of a PKA inhibitor. that acupuncture inhibits pCREB activation in the nucleus accumbens [45] and spinal cord [46] in drug addiction. This result indicates that acupuncture produces different effects on the expression of pCREB in different parts of the body for different diseases, in accordance with the holistic view of acupuncture treatment in the TCM theory.…”

Acupuncture reduces relapse to cocaine‐seeking behavior via activation of GABA neurons in the ventral tegmental area

“…The effects of acupuncture on cocaine‐induced locomotor activity, expression of phospho‐cyclic AMP response elements binding (pCREB) and c‐Fos in the NAc, release of GABA in the VTA and DA in the NAc and cocaine‐seeking behavior were investigated by manual acupuncture at bilateral HT7 acupuncture points in freely moving animals, as performed previously in our laboratory (Zhao et al ; Yoon et al ). HT7 acupoint on the heart channel has been used to treat mental and psychiatric disorders in clinic of oriental medicine.…”

Effects of Electroacupuncture on Methamphetamine‐Induced Behavioral Changes in Mice

“…Based on these findings, EA influences MAO-A expression maybe via regulating the inflammatory cytokines-related pathways. In addition, EA-related reduction in cocaine-induced behavioral sensitization is closely associated with the reduction of dopamine synthesis in the ventral tegmental area (VTA) region [17] and phosphorylated cAMP response element-binding protein expression in the NAc [8]. A study suggested that EA enhances extinction learning of heroin-induced seeking behavior, which may associate with cAMP downstream pathway—FosB expression in the NAc [40].…”

“…In 1979, the World Health Organization (WHO) provided a list of 40 diseases suitable for acupuncture treatment; these included heroin and cocaine dependence and abuse [7]. Some clinical and basic studies have suggested that acupuncture, as a therapeutic tool, is useful for reducing drug abuse-induced seeking behaviors and side effects by restoring cellular function imbalance in the central nervous system (CNS) [8–10]. Acupuncture at several specific acupoints could reduce cocaine-induced seizures, behavioral sensitization, stress-induced cocaine relapse, and METH-induced hyperactivity in rodent models [8–10].…”

“…Some clinical and basic studies have suggested that acupuncture, as a therapeutic tool, is useful for reducing drug abuse-induced seeking behaviors and side effects by restoring cellular function imbalance in the central nervous system (CNS) [8–10]. Acupuncture at several specific acupoints could reduce cocaine-induced seizures, behavioral sensitization, stress-induced cocaine relapse, and METH-induced hyperactivity in rodent models [8–10]. In addition, clinical studies have validated that electroacupuncture (EA) at Hegu (LI4) and Zusanli (ST36) can improve sleep latency in methadone maintenance therapeutic patients [11] and that three auricular sites and one body site on LI4 significantly decreases cocaine use in methadone-treated patients [12].…”