Inputs from the basolateral amygdala to the nucleus accumbens shell control opiate reward magnitude via differential dopamine D1 or D2 receptor transmission

Abstract

The basolateral amygdala (BLA), ventral tegmental area and nucleus accumbens (NAc) form a functionally connected neural circuit involved in the processing of opiate-related reward and memory. Dopamine (DA) projections from the ventral tegmental area to the BLA modulate associative plasticity mechanisms within the BLA. However, the role of DA receptor signaling in the BLA and its functional outputs to the NAc during opiate reward processing is not currently understood. Using an unbiased place conditioning procedure, we measured the rewarding effects of morphine following intra-BLA microinfusions of specific DA D1 or D2 receptor agonists in either opiate-naive or opiate-dependent/withdrawn rats. Activation of intra-BLA D1 receptors strongly potentiated the behaviorally rewarding effects of opiates, only in the opiate-naive state. However, once opiate dependence and withdrawal occurred, the intra-BLA DA-mediated potentiation of opiate reward salience switched to a D2 receptor-dependent substrate. We next performed single-unit, in-vivo extracellular neuronal recordings in the NAc shell (NA shell), to determine if intra-BLA D1/D2 receptor activation may modulate the NA shell neuronal response patterns to morphine. Consistent with our behavioral results, intra-BLA D1 or D2 receptor activation potentiated NAc 'shell' (NA shell) neuronal responses to sub-reward threshold opiate administration, following the same functional boundary between the opiate-naive and opiate-dependent/withdrawn states. Finally, blockade of N-methyl-d-aspartate transmission within the NA shell blocked intra-BLA DA D1 or D2 receptor-mediated opiate reward potentiation. Our findings demonstrate a novel and functional DA D1/D2 receptor-mediated opiate reward memory switch within the BLA→NA shell circuit that controls opiate reward magnitude as a function of opiate exposure state.

Cannabinoid Transmission in the Prelimbic Cortex Bidirectionally Controls Opiate Reward and Aversion Signaling through Dissociable Kappa Versus μ-Opiate Receptor Dependent Mechanisms

“…Adult male Sprague Dawley rats (350 -400 g; Charles River Canada) were anesthetized with an intraperitoneal injection of a ketamine (80 mg/ml)-xylazine (6 mg/kg) mixture, and placed in a stereotaxic device. For intra-PLC microinfusions, two stainless steel guide cannulae (22 gauge) were implanted into the PLC division of the mPFC using the following coordinates (15°angle): from bregma, anteroposterior (AP) ϩ2.9 mm, lateral (LAT) Ϯ1.9 mm, ventral (V) Ϫ3.0 mm from the dural surface (Laviolette and Grace, 2006). For experiments involving intra-PLC and intra-VTA microinfusions, rats received two additional cannulae implanted in the VTA using the following coordinates (10°angle): from bregma, AP Ϫ5.0 mm, LAT Ϯ2.3 mm, and V Ϫ8.0 mm from the dural surface.…”

“…These doses of intra-cranial WIN 55,212-2 are pharmacologically specific and can be blocked by coadministration of selective CB1 antagonists (Laviolette and Grace, 2006;Tan et al, 2011). First, challenging the motivational effects of a sub-threshold conditioning dose of morphine (0.05 mg/kg, i.p.…”

“…Thus, activation of CB1 transmission in the mPFC potentiates normally sub-threshold fear-memory formation behaviorally and associative neuronal conditioning (Laviolette and Grace, 2006). Cannabinoid transmission within the BLA also modulates fear memory processing via modulatory inputs to PLC neurons (Tan et al, 2010).…”

“…The interconnected ventral tegmental area (VTA) and medial prefrontal cortex (mPFC) contain high levels of CB1 receptors. CB1 receptor transmission within these regions can potently modulate rewarding and aversive motivational behaviors and memory formation (Laviolette and Grace, 2006;Zangen et al, 2006;Tan et al, 2010). For example, modulation of CB1 transmission within the prelimbic cortical (PLC) division of the mPFC, increases the emotional salience of fear-related stimuli (Laviolette and Grace, 2006;Tan et al, 2010).…”

“…The VTA serves as a critical neural region for the processing of opiate-related motivational information (Bozarth and Wise, 1981;Laviolette et al, 2004). Within the VTA, opiaterelated motivational processing is mediated via heterogeneous opiate-receptor populations.…”