No abstract

Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) are neurotrophic factors that are critical for the growth, survival, and differentiation of developing neurons. These neurotrophic factors also play important roles in the survival and function of adult neurons, learning and memory, and synaptic plasticity. Since the mid 1990s, investigators have studied the role of BDNF and GDNF in the behavioral effects of abused drugs and in the neuroadaptations induced by repeated exposure to drugs in the mesocorticolimbic dopamine system. Here, we review rodent studies on the role of BDNF and GDNF in drug reward, as assessed in the drug self-administration and the conditioned place preference procedures, and in drug relapse, as assessed in extinction and reinstatement procedures. Our main conclusion is that whether BDNF or GDNF would facilitate or inhibit drug-taking behaviors is dependent on the drug type, brain site, the addiction phase (initiation, maintenance, or abstinence/relapse), and the time interval between sitespecific BDNF or GDNF injections and the reward-and relapse-related behavioral assessments.

J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07502.x Abstract Heroin use has seriously threatened public heath in many countries, but the existing therapies continue to have many limitations. Recently, immunotherapy has shown efficacy in some clinical studies, including vaccines against nicotine and cocaine, but no opioid vaccines have been introduced in clinical studies. The development of a novel opioid antigen designed specifically for the prevention of heroin addiction is necessary. A morphine–keyhole limpet hemocyanin conjugate was prepared and administered subcutaneously in rats. Antibody titers in plasma were measured using an enzyme‐linked immunosorbent assay (ELISA). Competitive ELISA was used to assess the selectivity of the antibodies. Dopamine concentrations in the nucleus accumbens in rats after vaccine administration were determined by high‐performance liquid chromatography with electrochemical detection. The effects of the vaccine on the heroin‐primed restatement of self‐administration and locomotor sensitization were evaluated. A novel hapten, 6‐glutarylmorphine, was produced, and the vaccine generated a high antibody titer response. This vaccine displayed specificity for both morphine and heroin, but the anti‐morphine antibodies could not recognize dissimilar therapeutic opioid compounds, such as buprenorphine, methadone, naloxone, naltrexone, codeine, and nalorphine. The morphine antibody significantly decreased morphine‐induced locomotor activity in rats after immunization. Importantly, rats immunized with this vaccine did not exhibit heroin‐primed reinstatement of heroin seeking when antibody levels were sufficiently high. The vaccine reduced dopamine levels in the nucleus accumbens after morphine administration, which is consistent with its behavioral effects. These results suggest that immunization with a novel vaccine is an effective means of inducing a morphine‐specific antibody response that is able to attenuate the behavioral and psychoactive effects of heroin.