Mechanisms underlying controlled alcohol consumption: nociceptine/kappa-opioid related gene expression in the rat brain

Каппа-опиоидная и ноцицептиновая системы играют важную роль в модуляции функций дофаминергической системы «награды», однако их роль в механизмах формирования аддиктивного поведения до конца не ясна. Цель исследования: сравнить уровни мРНК каппа-опиоидного (OPRK1) и ноцицептинового (OPRL1) рецепторов, а также их эндогенных лигандов - препродинорфина (PDYN) и препроноцицептина (PDYN) в мозге животных с различным уровнем предпочтения алкоголя. Методы: потребление алкоголя у половозрелых крыс-самцов Wistar регистрировали с 60-го по 85-й дни жизни в модели «свободный выбор» между водой и 10% раствором этанола. Относительный уровень мРНК в структурах мозга определяли на 86-й день жизни методом ПЦР в реальном времени. Результаты: Экспрессия мРНК PDYN и PNOC в стриатуме, и OPRK1 и OPRL1 в миндалине была достоверно выше у «отвергающих», т.е. контролирующих потребление алкоголя на постоянно низком уровне животных, по сравнению с «предпочитающими», увеличившими потребление алкоголя в течение эксперимента. Заключение: более высокий уровень экспрессии генов эндогенных опиоидов PDYN и PNOC и их рецепторов в исследованных областях мозга может обусловливать меньшую гедоническую привлекательность алкоголя, играя превентивную роль и снижая риск злоупотребления алкоголем Kappa-opioidergic and nociceptinergic systems both inhibit the mesolimbic reward circuitry but their role in mechanisms of addictive behavior still is not well understood. Objective of the study was to compare expression of kappa opioid and nociceptin receptor genes (OPRK1 and OPRL1, respectively) and their endogenous ligands, preprodynorphin (PDYN) and prepronociceptin (PNOC), in the mesolimbic areas of rats with high and low voluntary alcohol consumption. Methods. Individually housed male Wistar rats were given a 25-day-long two-bottle (10% ethanol/water) free choice trial. mRNA levels were measured using the real-time polymerase chain reaction (qPCR). Results. Alcohol preferring rats progressively increased their ethanol consumption over the course of experiment while non-preferring, low-drinking animals controlled their alcohol intake near the baseline level. Alcohol non-preferring rats were identified to have significantly higher levels of PDYN and PNOC mRNA in the striatum and OPRK1 and OPRL1 mRNA in the amygdala compared to ethanol preferring animals. Conclusion. We suggested that higher levels of the “anti-reward opioid system” gene expression in mesolimbic structures may blunt the hedonic response to alcohol and thus preclude the increase in alcohol preference and uncontrolled excessive alcohol intake.

Free-Choice by the Rat of the Greater of Two Brightness Changes

In a previous experiment (2) it was shown that rats will choose that arm of a maze the brightness of which has been changed between an exposure trial and a free-choice trial. The present experiment tests the hypothesis, derivable in part from Glanzer's satiation theory, that if both arms are changed, rats will choose the arm representing the greater change. Ss were 28 male albino rats satiated for food and water. Four stimulus conditions were used, a condition being composed of two trials: on Trial 1 rats were exposed to 2 arms of a Y-maze for 3 min., but were prevented from entering either by means of glass partitions; for Trial 2 the brightnesses of both arms were changed and the partitions removed. In Condition I, the Trial 1 configuration was left-black, right-grey; on Trial 2 both arms were white. In Condition II, on Trial 1 the configuration was left-grey, right-black, and again on Trial 2 both arms were white. Conditions III and IV were analogous to I and II with white and grey on Trial 1, and both arms black on Trial 2. Of the 28 Ss, 20 made the predicted response, significant by the sign test (one tail) at better than the .02 level. Errors were distributed equally between Conditions I and II combined and III and IV combined, indicating that the grey arm was discriminable from both the white and black arms.