The role of orexin-1 receptors within the ventral tegmental area in the extinction and reinstatement of methamphetamine place preference. 2023

Ferdos Zamanirad, and Mojdeh Fattahi, and Haleh Amirteymori, and Zahra Mousavi, and Abbas Haghparast
Pharmacology and Toxicology Department, Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, the Islamic Republic of Iran.

Targeting the orexin system has recently been identified as one of the promising options for treating drug addiction. It may be more feasible and achievable if we investigate the accurate function of the orexin system in brain areas implicated in reward and addiction, such as the ventral tegmental area (VTA) by animal reward models. This study investigated the contribution of the orexin system, mainly the orexin-1 receptors (OX1R) in the VTA, in the extinction and reinstatement of methamphetamine (METH) related memories in the conditioned place preference (CPP) model. Animals after the acquisition of METH place preference were subjected to two separate sets of extinction and reinstatement experiments to receive various concentrations of selective OX1R antagonist, SB334867 into the bilateral VTA before extinction sessions (1, 3, and 10 nmol/0.3 μl DMSO per side) or only on the reinstatement phase (3, 10, and 30 nmol/0.3 μl DMSO per side), respectively. Intra-VTA infusion of SB334867 throughout the extinction phase could remarkably facilitate the extinction process and decrease the maintenance of reinforcing effects of METH at the highest dosage (10 nmol; p < 0.0001). Data also indicated a single microinfusion of SB334867 into the VTA before reinstatement of the METH-seeking behavior could considerably prevent the relapse of previously formed reward-context memories (10 nmol; p < 0.01 and 30 nmol; p < 0.001). The present study provided evidence supporting the potential therapeutic effects of the orexin system modulation, specifically in the VTA, on different stages of METH-induced place preference.

UI MeSH Term Description Entries
D008694 Methamphetamine A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. Deoxyephedrine,Desoxyephedrine,Desoxyn,Madrine,Metamfetamine,Methamphetamine Hydrochloride,Methylamphetamine,N-Methylamphetamine,Hydrochloride, Methamphetamine,N Methylamphetamine
D003216 Conditioning, Operant Learning situations in which the sequence responses of the subject are instrumental in producing reinforcement. When the correct response occurs, which involves the selection from among a repertoire of responses, the subject is immediately reinforced. Instrumental Learning,Learning, Instrumental,Operant Conditioning,Conditionings, Operant,Instrumental Learnings,Learnings, Instrumental,Operant Conditionings
D004121 Dimethyl Sulfoxide A highly polar organic liquid, that is used widely as a chemical solvent. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect tissue during CRYOPRESERVATION. Dimethyl sulfoxide shows a range of pharmacological activity including analgesia and anti-inflammation. DMSO,Dimethyl Sulphoxide,Dimethylsulfoxide,Dimethylsulphinyl,Dimethylsulphoxide,Dimexide,Rheumabene,Rimso,Rimso 100,Rimso-50,Sclerosol,Sulfinylbis(methane),Rimso 50,Rimso50,Sulfoxide, Dimethyl,Sulphoxide, Dimethyl
D005108 Extinction, Psychological The procedure of presenting the conditioned stimulus without REINFORCEMENT to an organism previously conditioned. It refers also to the diminution of a conditioned response resulting from this procedure. Psychological Extinction,Extinction (Psychology),Extinctions (Psychology),Extinctions, Psychological,Psychological Extinctions
D000068797 Orexins Neuropeptide hormones that play a role in regulating a variety of behavioral and physiological processes in response to motivational stimuli. Hypocretin,Orexin,Hypocretin-1,Hypocretin-2,Hypocretins,Orexin-A,Orexin-B,Hypocretin 1,Hypocretin 2,Orexin A,Orexin B
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
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar 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
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D064446 Orexin Receptors G-protein-coupled NEUROPEPTIDE RECEPTORS that have specificity for OREXINS and play a role in appetite control, and sleep-wake cycles. Two principle receptor types exist, each having a specificity for OREXIN A and OREXIN B peptide subtypes. Hypocretin Receptor,OX1 Receptor,OX2 Receptor,Orexin Receptor,HCRT Receptor 1,HCRT Receptor 2,HCTR2 Protein,Hypocretin Receptor 2,Hypocretin Receptors,Hypocretin Receptors 2,Hypocretin-1 Receptor,Hypocretin-2 Receptor,OX1 Receptors,OX2 Receptors,Orexin A Receptor,Orexin B Receptor,Orexin Receptor 2,Orexin Receptor Type 1,Orexin Receptor Type 2,Orexin-A Receptor,Orexin-A Receptors,Orexin-B Receptor,Orexin-B Receptors,Receptor 2, Hypocretin,Receptor, Orexin-A,Receptor, Orexin-B,Hypocretin 1 Receptor,Hypocretin 2 Receptor,Orexin A Receptors,Orexin B Receptors,Protein, HCTR2,Receptor 1, HCRT,Receptor 2, HCRT,Receptor 2, Orexin,Receptor, Hypocretin,Receptor, Hypocretin-1,Receptor, Hypocretin-2,Receptor, OX1,Receptor, OX2,Receptor, Orexin,Receptor, Orexin A,Receptor, Orexin B,Receptors 2, Hypocretin,Receptors, Hypocretin,Receptors, OX1,Receptors, OX2,Receptors, Orexin,Receptors, Orexin-A,Receptors, Orexin-B

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