A morphine/heroin vaccine with new hapten design attenuates behavioral effects in rats

• Published in: Journal of neurochemistry 2011-12, Vol.119 (6), p.1271-1281
• Main Authors: Li, Qian‐Qian, Luo, Yi‐Xiao, Sun, Cheng‐Yu, Xue, Yan‐Xue, Zhu, Wei‐Li, Shi, Hai‐Shui, Zhai, Hai‐Feng, Shi, Jie, Lu, Lin
• Format: Article
• Language: English
• Subjects: addiction; Animals; Antibodies - blood; Antibodies - immunology; Antibody response; Antibody Specificity; Biological and medical sciences; Buprenorphine; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Chromatography, High Pressure Liquid; Clinical trials; Cocaine; Codeine; Conditioning, Operant - drug effects; Conditioning, Operant - physiology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Dopamine; Dopamine - metabolism; Drug self-administration; Enzyme-Linked Immunosorbent Assay; Extinction, Psychological - drug effects; Extinction, Psychological - physiology; Fundamental and applied biological sciences. Psychology; Haptens; Hemocyanins; Hemocyanins - administration & dosage; Heroin; Heroin - administration & dosage; Heroin - immunology; Heroin Dependence - blood; Heroin Dependence - immunology; Heroin Dependence - therapy; immunization; Immunoassay; Immunotherapy; Locomotor activity; Male; Medical sciences; Morphine; morphine/heroin; Motor Activity - immunology; Motor Activity - physiology; Narcotics; Neurochemistry; Neurology; Nicotine; Nucleus accumbens; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Opioids; Rats; Rats, Sprague-Dawley; Reinforcement (Psychology); Reinstatement; Self Administration; Substance abuse treatment; vaccine; Vaccines; Vaccines, Conjugate - administration & dosage; Vaccines, Conjugate - chemistry; Vaccines, Conjugate - immunology; Vertebrates: nervous system and sense organs
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2011.07502.x

J. Neurochem. (2011) 10.1111/j.1471‐4159.2011.07502.x 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. Novel vaccine blocks morphine/heroin relapse 
Immunotherapy has shown efficacy in preventing nicotine and cocaine relapse in clinical trials. Here reported a novel morphine conjugate vaccine, including a novel hapten, 6‐glutarylmorphin, with keyhole limpet hemocyanin (KLH), triggered a robust and specific antibody response sufficient to attenuate behavioral and psychoactive effects of morphine/heroin in rats. This vaccine might potentially be implicated in the clinical treatment of