Department of Neurobiology & Behavior, University of California, 1203 McGaugh Hall, Irvine, CA, 92697, USA.
Department of Anatomy & Neurobiology, University of California, Irvine, CA, USA.
Psychopharmacology (Berl). 2018 Jan;235(1):121-134. doi: 10.1007/s00213-017-4749-8. Epub 2017 Oct 11.
Adolescence is characterized by endocannabinoid (ECB)-dependent refinement of neural circuits underlying emotion, learning, and motivation. As a result, adolescent cannabinoid receptor stimulation (ACRS) with phytocannabinoids or synthetic agonists like "Spice" cause robust and persistent changes in both behavior and circuit architecture in rodents, including in reward-related regions like medial prefrontal cortex and nucleus accumbens (NAc).
Here, we examine persistent effects of ACRS with the cannabinoid receptor 1/2 specific agonist WIN55-212,2 (WIN; 1.2 mg/kg/day, postnatal day (PD) 30-43), on natural reward-seeking behaviors and ECB system function in adult male Long Evans rats (PD 60+).
WIN ACRS increased palatable food intake, and altered attribution of incentive salience to food cues in a sign-/goal-tracking paradigm. ACRS also blunted hunger-induced sucrose intake, and resulted in increased anandamide and oleoylethanolamide levels in NAc after acute food restriction not seen in controls. ACRS did not affect food neophobia or locomotor response to a novel environment, but did increase preference for exploring a novel environment.
These results demonstrate that ACRS causes long-term increases in natural reward-seeking behaviors and ECB system function that persist into adulthood, potentially increasing liability to excessive natural reward seeking later in life.
青春期的特点是内源性大麻素(ECB)依赖于神经回路的精细调整,这些神经回路与情绪、学习和动机有关。因此,植物大麻素或合成激动剂如“香料”对青少年大麻素受体的刺激(ACRS)会导致啮齿动物的行为和回路结构发生强烈而持久的变化,包括在与奖励相关的区域,如内侧前额叶皮层和伏隔核(NAc)。
在这里,我们研究了大麻素受体 1/2 特异性激动剂 WIN55-212,2(WIN;1.2 mg/kg/天,出生后第 30-43 天)对成年雄性长耳大仓鼠(PD 60+)的自然奖励寻求行为和 ECB 系统功能的持久影响。
WIN ACRS 增加了美味食物的摄入量,并在标志/目标跟踪范式中改变了对食物线索的激励价值的归因。ACRS 还抑制了饥饿引起的蔗糖摄入,并导致急性食物限制后 NAc 中的花生四烯酸和油酰乙醇酰胺水平升高,而对照组则没有这种情况。ACRS 不影响食物厌恶或对新环境的运动反应,但确实增加了对探索新环境的偏好。
这些结果表明,ACRS 导致长期增加自然奖励寻求行为和 ECB 系统功能,这些影响持续到成年期,可能会增加以后过度追求自然奖励的倾向。