Psychopharmacology · 2002
Antalarmin, a putative CRH-RI antagonist, has transient reinforcing effects in rhesus monkeys.
Сравнительное исследованиеСтатьяПоддержка службы здравоохранения СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Broadbear Jillian H, Winger Gail, Rice Kenner C, Woods James H
Аннотация
RATIONALE: During the course of our investigation of antalarmin, a corticotropin-releasing hormone (CRH) antagonist, in rhesus monkeys, we noticed that large, intravenous doses of antalarmin resulted in behavioral changes that resembled intoxication.
OBJECTIVES: Antalarmin was evaluated in rhesus monkeys for its reinforcing effectiveness as well as for its effects on hypothalamic-pituitary-adrenal (HPA) axis activity.
METHODS: Twelve monkeys, each with a surgically implanted indwelling venous catheter, were trained to respond for and receive the short-acting barbiturate, methohexital. Monkeys responded on one of two schedules: a fixed ratio (FR) 10 (30 or 100), timeout (TO) 10 s schedule on which they received methohexital, antalarmin, vehicle or saline injections; or an FR30, TO 45 s during which saline, vehicle, or four different doses of methohexital or antalarmin were available. Each dose was available during a 25-min period separated by a 10-min TO. Blood samples were obtained from three monkeys before, during and after the self-administration sessions and assayed for ACTH and cortisol.
RESULTS: Antalarmin initially served as a reinforcer in 11 of 12 monkeys, although its reinforcing effects dissipated after three to four exposures under both operant schedules. Self-injection of antalarmin did not produce any change in cortisol levels, although methohexital did attenuate ACTH and cortisol release.
CONCLUSIONS: This study provides the first evidence for transient reinforcing properties of a putative centrally acting CRH-R1 selective antagonist.
OBJECTIVES: Antalarmin was evaluated in rhesus monkeys for its reinforcing effectiveness as well as for its effects on hypothalamic-pituitary-adrenal (HPA) axis activity.
METHODS: Twelve monkeys, each with a surgically implanted indwelling venous catheter, were trained to respond for and receive the short-acting barbiturate, methohexital. Monkeys responded on one of two schedules: a fixed ratio (FR) 10 (30 or 100), timeout (TO) 10 s schedule on which they received methohexital, antalarmin, vehicle or saline injections; or an FR30, TO 45 s during which saline, vehicle, or four different doses of methohexital or antalarmin were available. Each dose was available during a 25-min period separated by a 10-min TO. Blood samples were obtained from three monkeys before, during and after the self-administration sessions and assayed for ACTH and cortisol.
RESULTS: Antalarmin initially served as a reinforcer in 11 of 12 monkeys, although its reinforcing effects dissipated after three to four exposures under both operant schedules. Self-injection of antalarmin did not produce any change in cortisol levels, although methohexital did attenuate ACTH and cortisol release.
CONCLUSIONS: This study provides the first evidence for transient reinforcing properties of a putative centrally acting CRH-R1 selective antagonist.
Предметные рубрики MeSH
Adrenocorticotropic HormoneAnesthetics, IntravenousAnimalsDose-Response Relationship, DrugDrug Administration ScheduleHydrocortisoneHypothalamo-Hypophyseal SystemMacaca mulattaMaleMethohexitalPyrimidinesPyrrolesReceptors, Corticotropin-Releasing HormoneReinforcement, PsychologySelf AdministrationTime Factors