مورد إلكتروني
Lack of CB1 cannabinoid receptor impairs cocaine self-administration.
| العنوان: | Lack of CB1 cannabinoid receptor impairs cocaine self-administration. |
|---|---|
| المصدر: | Biological psychiatry, 30 (9 |
| بيانات النشر: | 2005-09 |
| تفاصيل مُضافة: | Soria, Guadalupe Mendizábal, Victoria Touriño, Clara Robledo, Patricia Ledent, Catherine Parmentier, Marc Maldonado, Rafael Valverde, Olga |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Acute rewarding properties are essential for the establishment of cocaine addiction, and multiple neurochemical processes participate in this complex behavior. In the present study, we used the self-administration paradigm to evaluate the role of CB1 cannabinoid receptors in several aspects of cocaine reward, including acquisition, maintenance, and motivation to seek the drug. For this purpose, both CB1 receptor knockout mice and wild-type littermates were trained to intravenously self-administer cocaine under different schedules. Several cocaine training doses (0.32, 1, and 3.2 mg/kg/infusion) were used in the acquisition studies. Only 25% of CB1 knockout mice vs 75% of their wild-type littermates acquired a reliable operant responding to self-administer the most effective dose of cocaine (1 mg/kg/infusion), and the number of sessions required to attain this behavior was increased in knockout mice. Animals reaching the acquisition criteria were evaluated for the motivational strength of cocaine as a reinforcer under a progressive ratio schedule. The maximal effort to obtain a cocaine infusion was significantly reduced after the genetic ablation of CB1 receptors. A similar result was obtained after the pharmacological blockade of CB1 receptors with SR141716A in wild-type mice. Moreover, the cocaine dose-response curve was flattened in the knockout group, suggesting that the differences observed between genotypes were related to changes in the reinforcing efficacy of the training dose of cocaine. Self-administration for water and food was not altered in CB1 knockout mice in any of the reinforcement schedules used, which emphasizes the selective impairment of drug reinforcement in these knockout mice. Finally, cocaine effects on mesolimbic dopaminergic transmission were evaluated by in vivo microdialysis in these mice. Acute cocaine administration induced a similar enhancement in the extracellular levels of dopamine in the nucleus accumbens of both CB1 knockout and wi Comparative Study Journal Article Research Support, Non-U.S. Gov't info:eu-repo/semantics/published |
| مصطلحات الفهرس: | Sciences bio-médicales et agricoles, Analysis of Variance, Anesthetics, Local -- administration & dosage, Animals, Behavior, Animal -- physiology, Cocaine -- administration & dosage, Conditioning, Operant -- drug effects, Dopamine -- metabolism, Dose-Response Relationship, Drug, Drug Administration Schedule, Feeding Behavior -- physiology, Food Deprivation -- physiology, Mice, Mice, Knockout, Microdialysis -- methods, Piperidines -- administration & dosage, Pyrazoles -- administration & dosage, Receptor, Cannabinoid, CB1 -- antagonists & inhibitors, Receptor, Cannabinoid, CB1 -- deficiency, Self Administration, Time Factors, Water Deprivation -- physiology, CB1 cannabinoid receptor, Cocaine, Dopamine, In vivo microdialysis, Knockout, Self-administration, info:eu-repo/semantics/article, info:ulb-repo/semantics/articlePeerReview, info:ulb-repo/semantics/openurl/article |
| URL: | |
| الإتاحة: | Open access content. Open access content 1 full-text file(s): info:eu-repo/semantics/restrictedAccess |
| ملاحظة: | 1 full-text file(s): application/pdf English |
| أرقام أخرى: | EQY oai:dipot.ulb.ac.be:2013/52321 uri/info:doi/10.1038/sj.npp.1300707 uri/info:pii/1300707 uri/info:pmid/15742004 uri/info:scp/27344432763 1363712222 |
| المصدر المساهم: | UNIVERSITE LIBRE DE BRUXELLES From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1363712222 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |