It is important to take governance classification into account when investigating variation in services, resources, or performance of governmental public health systems. As public health systems and services researchers seek to identify best practices in the organization of public health systems, consistent definition of different types of organization is critical. This system provides an objective and reliable system for classifying governance relationships that allows for comparisons that are meaningful to both practitioners and researchers.

Conditioned responding can be renewed by re-exposure to the conditioning context following extinction in a different context (ABA renewal) or by removal from the extinction context (AAB or ABC renewal). ABA renewal is robust in Pavlovian and operant conditioning paradigms. However, fewer studies have investigated AAB and ABC renewal of appetitive conditioning, and those that did predominantly used operant conditioning tasks. Renewal has theoretical relevance for extinction and for exposurebased treatments for substance use disorders that aim to extinguish reactivity to drug-predictive cues. We therefore investigated ABA, AAB, and ABC renewal of Pavlovian conditioned responding to cues that predicted either alcohol or sucrose. Male, Long-Evans rats (Charles River) were exposed to either 15% ethanol (Study 1: "alcohol") or 10% sucrose (Study 2: "sucrose") in their home cages. Next, they were trained to discriminate between two auditory stimuli (white noise and clicker; 10 s) in conditioning chambers equipped with distinct olfactory, visual, and tactile contextual stimuli (context A). One conditioned stimulus (CS+) was paired with fluid delivery (0.2 ml/CS+; 3.2 ml/session; alcohol or sucrose in separate experiments), and the second CS (CS−) was not. In all sessions (conditioning, extinction, and test), each CS was presented 16 times/session on a variable-time 67-s schedule, and entries into the fluid port were recorded. CS+ port entries were then extinguished by withholding fluid delivery either in context A or in a second, different context (context B). Next, we assessed ABA, AAB, and ABC renewal in the absence of fluid delivery. During extinction, CS+ port entries were initially elevated in context A relative to context B. ABA renewal of CS+ port entries occurred in both alcohol-and sucrose-trained rats. ABC renewal approached statistical significance when data from both experiments were combined. No AAB renewal was observed, and, in fact, alcohol-trained rats showed AAB suppression. These results corroborate the reliability of ABA renewal and suggest that ABC renewal is a modest effect that may require greater statistical power to detect. From a treatment perspective, the lack of AAB renewal suggests that exposure-based treatments for substance use disorders might benefit from implementation in real-world, drug-use contexts.

Contexts associated with prior reinforcement can renew extinguished conditioned responding. The prelimbic (PL) and infralimbic (IL) cortices are thought to mediate the expression and suppression of conditioned responding, respectively. Evidence suggests that PL inputs to the paraventricular nucleus of the thalamus (PVT) drive the expression of cue-induced reinstatement of drug seeking and that IL inputs to the PVT mediate fear extinction retrieval. However, the role of these projections in renewal of appetitive Pavlovian conditioned responding is unknown. We trained male and female Long-Evans rats to associate a conditioned stimulus (CS; 10 s white noise) with delivery of a 10% sucrose unconditioned stimulus (US; .2 ml/CS) to a fluid port in a distinct context (Context A). We then extinguished responding by presenting the CS without the US in a different context (Context B). At test, rats were returned to Context A, and optogenetic stimulation was delivered to either the IL-to-PVT or PL-to-PVT pathway during CS presentations. Optically stimulating the IL-to-PVT, but not the PL-to-PVT pathway, attenuated ABA renewal of CS port entries, and this effect was similar in males and females. Further, rats self-administered optical stimulation of the IL-to-PVT but not the PL-to-PVT pathway suggesting that activation of the IL-to-PVT pathway is reinforcing. The effectiveness of optical stimulation parameters to activate neurons in the IL, PL and PVT was confirmed using Fos immunohistochemistry. These findings provide evidence for novel neural mechanisms in renewal of responding to a sucrose-predictive CS, as well as more generally in contextual processing and appetitive associative learning.K E Y W O R D S extinction, Pavlovian conditioning, reward, sucrose, ventromedial prefrontal cortex Abbreviations: aPVT, anterior paraventricular nucleus of the thalamus; AAV, adeno-associated virus; ChR2, channelrhodopsin-2; CS, conditioned stimulus; eYFP, enhanced yellow fluorescent protein; IL, infralimbic; ITI, intertrial interval; mPVT, middle paraventricular nucleus of the thalamus; OFC, orbitofrontal cortex; PL, prelimbic; pPVT, posterior paraventricular nucleus of the thalamus; PVT, paraventricular nucleus of the thalamus; US, unconditioned stimulus.

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Renewal is the return of extinguished responding after removal from the extinction context. Renewal has been extensively studied using classical aversive conditioning procedures that measure a passive freezing response to an aversive conditioned stimulus. However, coping responses to aversive stimuli are complex and can be reflected in passive and active behaviours. Using the shock-probe defensive burying task, we investigated whether different coping responses are susceptible to renewal. During conditioning, male, Long-Evans rats were placed into a specific context (context A) where an electrified shock-probe delivered a 3 mA shock upon contact. During extinction, the shock-probe was unarmed in either the same (context A) or a different context (context B). Renewal of conditioned responses was assessed in the conditioning context (ABA) or in a novel context (ABC or AAB). Renewal of passive coping responses, indicated by an increased latency and a decreased duration of shock-probe contacts, was observed in all groups. However, renewal of passive coping, measured by increased time spent on the side of the chamber opposite the shock- probe, was only found in the ABA group. Renewal of active coping responses linked to defensive burying was not observed in any group. The present findings highlight the presence of multiple psychological processes underlying even basic forms of aversive conditioning and demonstrate the importance of assessing a broader set of behaviours to tease apart these different underlying mechanisms. The current findings suggest that passive coping responses may be more reliable indicators for assessing renewal than active coping behaviours associated with defensive burying.

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Extinction is a fundamental form of inhibitory learning that is important for adapting to changing environmental contingencies. While numerous studies have investigated the neural correlates of extinction using Pavlovian fear conditioning and appetitive operant reward-seeking procedures, less is known about the neural circuitry mediating the extinction of appetitive Pavlovian conditioned responding. Here, we aimed to generate an extensive brain activation map of extinction learning in a rat model of appetitive Pavlovian conditioning. Male Long-Evans rats were trained to associate a conditioned stimulus (CS; 20 s white noise) with the delivery of a 10% sucrose unconditioned stimulus (US; 0.3 ml/CS) to a fluid port. Control groups also received CS presentations, but sucrose was delivered either during the inter-trial interval or in the home-cage. After conditioning, 1 or 6 extinction sessions were conducted in which the CS was presented but sucrose was withheld. We performed Fos immunohistochemistry and network connectivity analyses on a set of cortical, striatal, thalamic, and amygdalar brain regions. Neural activity in the prelimbic cortex, ventral orbitofrontal cortex, nucleus accumbens core, and paraventricular nucleus of the thalamus was greater during recall relative to extinction. Conversely, prolonged extinction following 6 sessions induced increased neural activity in the infralimbic cortex, medial orbitofrontal cortex, and nucleus accumbens shell compared to home-cage controls. All these structures were similarly recruited during recall on the first extinction session. These findings provide novel evidence for the contribution of brain areas and neural networks that are differentially involved in the recall versus extinction of appetitive Pavlovian conditioned responding.