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Chronic morphine administration decreases the size of dopamine (DA) neurons in the ventral tegmental area (VTA). These transient morphological changes are accompanied by a reduced sensitivity of morphine-induced conditioned place preference (CPP) after chronic exposure to the drug. In this study we examined alterations in the firing rate of DAergic neurons by means of extracellular recording following chronic morphine exposure and applied 100 Hz electroacupuncture (EA) treatment to reverse the reduced firing rate of these neurons. In the first set of experiments we show that in rats, which received chronic morphine treatment for 14 days, a small dose of morphine was not able to induce a CPP response anymore. However, the sensitivity to morphine was reinstated by consecutive EA treatment for 10 days. The electrophysiological response of VTA DA neurons to morphine was markedly reduced in chronic morphine-treated rats compared to saline-treated controls. A substantial recovery of the reactivity of VTA DA neurons to morphine was observed in rats that received 100 Hz EA for 10 days. Our findings suggest that 100 Hz EA is a potential therapy for the treatment of opiate addiction by normalizing the activity of VTA DA neurons.

Glutamate receptors are known to be densely distributed in the forebrain rewarding circuits, and glutamatergic transmission is actively involved in the regulation of rewarding and reinstating effects of drugs of abuse. Here we investigated the possible involvement of the N -methyl- d -aspartate (NMDA) receptors in the reinstatement of extinguished morphine conditioned place preference (CPP) in rats. We found that previously extinguished morphine (3 mg/kg, i.p.) CPP was markedly reinstated by a priming injection of morphine (2 mg/kg, i.p.) or an acute environmental stressor (forced swim for 10 min), but not by the stress induced by a 24-h food deprivation. Parallel with this, protein levels of the NMDA receptor 2B subunit (NR2B) were elevated in the nucleus accumbens (NAc) and the hippocampus, but not the prefrontal cortex, of reinstated rats. Systemic administration of an NR2B selective antagonist ifenprodil (1, 3, 10 mg/kg, i.p.) attenuated the reinstatement induced by a priming morphine injection, although not by the forced swim. Ifenprodil (2.0 μg/rat) directly injected into the NAc shell or the CA1 region of the dorsal hippocampus produced a similar effect. These results indicate that the NR2B-containing NMDA receptors in the NAc and the dorsal hippocampus play a significant role in mediating the reinstatement of rewarding responses to morphine.

Electroacupuncture (EA) has been used to suppress heroin craving in addicts and the conditioned place preference (CPP) for morphine in the rat. The question remained whether EA by itself will produce some rewarding effect. This was investigated using the CPP procedure in the present study. The results indicated that rats showed a significant preference to the 2 Hz EA-paired compartment. This rewarding effect of EA was prevented by pre-treatment with the opioid receptor antagonist naloxone [2 mg kg−1, intraperitoneally (i.p.)], CB1 cannabinoid antagonist AM251 (3 μg per rat, intracerebroventricularly) or D1 dopamine receptor antagonist SCH23390 (0.1 mg kg−1, i.p.), respectively. TempspacetempspaceIt is concluded that 2 Hz EA is capable of inducing CPP in the rat via the activation of the endogenous opioid-, cannabinoid- and dopamine-systems.

The aim of this study was to observe the effect of electroacupuncture (EA) on chronic morphine-induced neuronal morphological changes in the ventral tegmental area (VTA) in rats at electron-microscopic level. Fourteen days of administering escalating doses of morphine induced pathological morphological changes of neurons in the VTA: the rough endoplasmic reticulum swelled, membrane configuration of the nucleus and mitochondria blurred, and structure of myelin sheath changed. Both 2 and 100 Hz EA treatment reversed the morphological alterations induced by chronic morphine administration. The findings provide new evidence that EA may serve as a potential therapy in treating opiate addiction.

Chronic morphine administration induces functional and morphological alterations in the mesolimbic dopamine system (MLDS), which is believed to be the neurobiological substrate of opiate addiction. Our previous studies have demonstrated that peripheral electrical stimulation (PES) can suppress morphine withdrawal syndrome and morphine-induced conditioned place preference (CPP) in rats. The present study was designed to investigate if PES could reverse the cell size reduction induced by chronic morphine treatment in the ventral tegmental area (VTA), which is an important area of the MLDS. Immunohistochemical observations showed that the cell size of dopaminergic neurons in the VTA reduced significantly in the chronic morphine treated rats with a concomitant decrease in the number of BDNF-positive cells compared to saline-treated rats. A much milder morphological change, accompanying with an increased number of BDNF-positive cells, was observed in dopaminergic neurons in the rats that received repeated 100 Hz PES after morphine withdrawal. In another experiment, enzyme-linked immunosorbent assay (ELISA) reconfirmed a significant up-regulation of BDNF protein level in the VTA in the rats received 100 Hz PES after morphine abstinence. These results demonstrate for the first time that the PES could facilitate the morphological recovery of the VTA dopaminergic cells damaged by chronic morphine treatment and up-regulated the BDNF protein level in the VTA. Activation of endogenous BDNF by PES may play a role in the recovery of the injured dopaminergic neurons, thus underlying the effectiveness of PES in the treatment of morphine addiction.

A Be δ-doped GaAs/AlAs three quantum wells emitter in the terahertz range is fabricated and electroluminescence is investigated. An electroluminescence peak centered at 23.4 meV with a full width at half maximum of 4.2 meV is observed under a bias of 2 V at low temperature (T=4.5 K). The emission peak is attributed to the 2p to 1s internal transitions of the Be acceptors in the center of δ-doped GaAs quantum well. The current-voltage characteristics of the device measured at different temperatures demonstrate a strong negative differential resistance and temperature dependence.