LeCocq Mandy Rita, Mainville-Berthiaume Amélie, Laplante Isabel, Samaha Anne-Noël
Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
Neural Signaling and Circuitry Research Group (SNC), Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.
Int J Neuropsychopharmacol. 2025 Jun 6;28(6). doi: 10.1093/ijnp/pyaf030.
Reward-associated cues guide reward-seeking behaviors. These cues include conditioned stimuli (CSs), which occur following seeking actions and predict reward delivery, and discriminative stimuli (DSs), which occur response-independently and signal that a seeking action will produce reward. Metabotropic group II glutamate (mGlu2/3) receptors in the basolateral amygdala (BLA) modulate CS-guided reward seeking; however, their role in DS effects is unknown.
We developed a procedure to assess DS and CS effects on reward seeking in the same subjects within the same test session. Female and male rats self-administered sucrose where DSs signaled periods of sucrose availability (DS+) and unavailability (DS-). During DS+ trials, lever presses produced sucrose paired with a CS+. During DS- trials, lever presses produced a CS- and no sucrose. Across 14 sessions, rats learned to load up on sucrose during DS+ trials and inhibit responding during DS- trials. We then determined the effects of intra-BLA microinfusions of the mGlu2/3 receptor agonist LY379268 on cue-evoked sucrose seeking during a test where the DSs and CSs were presented response-independently, without sucrose. Before testing, rats received intra-BLA microinjections of artificial cerebrospinal fluid (aCSF) or LY379268.
Under aCSF, only the DS+ and DS+CS+ combination triggered increases in reward-seeking behavior. The CS+ alone was ineffective. Intra-BLA LY379268 suppressed the increases in sucrose seeking triggered by the DS+ and DS+CS+ combination.
Using a new procedure to test reward seeking induced by DSs and CSs, we show that BLA mGlu2/3 receptor activity mediates the incentive motivational effects of reward-predictive DSs.
与奖励相关的线索引导着寻求奖励的行为。这些线索包括条件刺激(CSs),它在寻求行为之后出现并预测奖励的给予,以及辨别性刺激(DSs),它独立于反应而出现并表明寻求行为将产生奖励。基底外侧杏仁核(BLA)中的代谢型II组谷氨酸(mGlu2/3)受体调节由CS引导的奖励寻求;然而,它们在DS效应中的作用尚不清楚。
我们开发了一种程序,以在同一测试时段内评估DS和CS对同一受试者奖励寻求的影响。雌性和雄性大鼠自行摄入蔗糖,其中DSs表明蔗糖可获得期(DS+)和不可获得期(DS-)。在DS+试验期间,按压杠杆会产生与CS+配对的蔗糖。在DS-试验期间,按压杠杆会产生CS-且无蔗糖。在14个时段中,大鼠学会在DS+试验期间大量摄入蔗糖,并在DS-试验期间抑制反应。然后,在一个测试中,我们确定了向BLA内微量注射mGlu2/3受体激动剂LY379268对线索诱发的蔗糖寻求的影响,在该测试中,DSs和CSs独立于反应呈现,且无蔗糖。在测试前,大鼠接受向BLA内微量注射人工脑脊液(aCSF)或LY379268。
在aCSF条件下,只有DS+和DS+CS+组合会引发奖励寻求行为的增加。单独的CS+无效。向BLA内注射LY-379268可抑制由DS+和DS+CS+组合引发的蔗糖寻求增加。
使用一种新的程序来测试由DSs和CSs诱发的奖励寻求,我们表明BLA mGlu2/3受体活性介导了奖励预测性DSs的激励动机效应。