Electrophysiological characterization of harmane-induced activation of mesolimbic dopamine neurons. 2010

Ouafa Arib, and Pascal Rat, and Robert Molimard, and Abderrahman Chait, and Philippe Faure, and Renaud de Beaurepaire
Laboratoire de Psychopharmacologie, Centre Hospitalier Paul Guiraud, 54 avenue de la République, 94806 Villejuif, France.

It has been suggested that the beta-carbolines harmane and norharmane may be involved in the pathophysiology of Parkinson's disease, psychosis and addiction, but the mechanisms of these possible effects remain to be elucidated. In the present study, the effects of the two compounds were examined by using in vivo extracellular recordings of ventral tegmental dopamine neurons. The effects of harmane (2mg/kg) and norharmane (2mg/kg), were compared to those of nicotine (11microg/kg), of cotinine (0.5mg/kg), of the monoamine-oxidase-A inhibitor befloxatone (0.12mg/kg), and of the monoamine-oxidase-B inhibitor selegiline (0.5mg/kg). The effects of harmane were also tested after pre-treatment with the nicotine receptor antagonist mecamylamine. The results show that all substances, except befloxatone, activate the firing and/or burst activity of dopamine neurons. The increase in firing rate produced by harmane was approximately 18 times greater than that produced by nicotine. Such powerful excitation of dopamine neurons by harmane may in part explain its involvement in neurotoxicity, psychosis and addiction. The absence of effect of befloxatone supports the hypothesis that the effect of harmane is not related to its monoamine-oxidase-A inhibitory properties. Mecamylamine inhibited by approximately 80% the activity of harmane, indicating that the activating effect of harmane on dopamine neurons involves several mechanisms, among which activation of nicotinic receptors likely has a prominent importance. The results of the present study support the hypothesis that harmane could be a tobacco (or smoke) component other than nicotine involved in tobacco dependence.

UI MeSH Term Description Entries
D008297 Male Males
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D009714 Nucleus Accumbens Collection of pleomorphic cells in the caudal part of the anterior horn of the LATERAL VENTRICLE, in the region of the OLFACTORY TUBERCLE, lying between the head of the CAUDATE NUCLEUS and the ANTERIOR PERFORATED SUBSTANCE. It is part of the so-called VENTRAL STRIATUM, a composite structure considered part of the BASAL GANGLIA. Accumbens Nucleus,Nucleus Accumbens Septi,Accumbens Septi, Nucleus,Accumbens Septus, Nucleus,Accumbens, Nucleus,Nucleus Accumbens Septus,Nucleus, Accumbens,Septi, Nucleus Accumbens,Septus, Nucleus Accumbens
D002243 Carbolines A group of pyrido-indole compounds. Included are any points of fusion of pyridine with the five-membered ring of indole and any derivatives of these compounds. These are similar to CARBAZOLES which are benzo-indoles. Carboline,Pyrido(4,3-b)Indole,Beta-Carbolines,Pyrido(4,3-b)Indoles,Beta Carbolines
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006247 Harmine Alkaloid isolated from seeds of PEGANUM HARMALA; ZYGOPHYLLACEAE. It is identical to banisterine, or telepathine, from Banisteria caapi and is one of the active ingredients of hallucinogenic drinks made in the western Amazon region from related plants. It has no therapeutic use, but (as banisterine) was hailed as a cure for postencephalitic PARKINSON DISEASE in the 1920's. 9H-Pyrido(3,4-b)indole, 7-methoxy-1-methyl-,Banisterine,Leucoharmine,Telepathine,Yageine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D017557 Ventral Tegmental Area A region in the MESENCEPHALON which is dorsomedial to the SUBSTANTIA NIGRA and ventral to the RED NUCLEUS. The mesocortical and mesolimbic dopaminergic systems originate here, including an important projection to the NUCLEUS ACCUMBENS. Overactivity of the cells in this area has been suspected to contribute to the positive symptoms of SCHIZOPHRENIA. Area Tegmentalis Ventralis,Ventral Tegmental Area of Tsai,Area Tegmentalis Ventrali,Tegmental Area, Ventral,Tegmentalis Ventrali, Area,Tegmentalis Ventralis, Area

Related Publications

Ouafa Arib, and Pascal Rat, and Robert Molimard, and Abderrahman Chait, and Philippe Faure, and Renaud de Beaurepaire
December 1994, The Journal of pharmacology and experimental therapeutics,
Ouafa Arib, and Pascal Rat, and Robert Molimard, and Abderrahman Chait, and Philippe Faure, and Renaud de Beaurepaire
May 1998, Brain research,
Ouafa Arib, and Pascal Rat, and Robert Molimard, and Abderrahman Chait, and Philippe Faure, and Renaud de Beaurepaire
December 2008, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Ouafa Arib, and Pascal Rat, and Robert Molimard, and Abderrahman Chait, and Philippe Faure, and Renaud de Beaurepaire
November 1984, Neuropharmacology,
Ouafa Arib, and Pascal Rat, and Robert Molimard, and Abderrahman Chait, and Philippe Faure, and Renaud de Beaurepaire
January 1988, Synapse (New York, N.Y.),
Ouafa Arib, and Pascal Rat, and Robert Molimard, and Abderrahman Chait, and Philippe Faure, and Renaud de Beaurepaire
January 2011, Addiction biology,
Ouafa Arib, and Pascal Rat, and Robert Molimard, and Abderrahman Chait, and Philippe Faure, and Renaud de Beaurepaire
July 2008, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Ouafa Arib, and Pascal Rat, and Robert Molimard, and Abderrahman Chait, and Philippe Faure, and Renaud de Beaurepaire
September 1980, Experientia,
Ouafa Arib, and Pascal Rat, and Robert Molimard, and Abderrahman Chait, and Philippe Faure, and Renaud de Beaurepaire
January 1977, Advances in biochemical psychopharmacology,
Ouafa Arib, and Pascal Rat, and Robert Molimard, and Abderrahman Chait, and Philippe Faure, and Renaud de Beaurepaire
November 1976, European journal of pharmacology,
Copied contents to your clipboard!