Dissociable dopaminergic and pavlovian influences in goal-trackers and sign-trackers on a model of compulsive checking in OCD.

RATIONALE: Checking is a functional behaviour that provides information to guide behaviour. However, in obsessive-compulsive disorder (OCD), checking may escalate to dysfunctional levels. The processes underpinning the transition from functional to dysfunctional checking are unclear but may be associated with individual differences that support the development of maladaptive behaviour. We examined one such predisposition, sign-tracking to a pavlovian conditioned stimulus, which we previously found associated with dysfunctional checking. How sign-tracking interacts with another treatment with emerging translational validity for OCD-like checking, chronic administration of the dopamine D2 receptor agonist quinpirole, is unknown. OBJECTIVES: We tested how functional and dysfunctional checking in the rat observing response task (ORT) was affected by chronic quinpirole administration in non-autoshaped controls and autoshaped animals classified as sign-trackers or goal-trackers. METHODS: Sign-trackers or goal-trackers were trained on the ORT before the effects of chronic quinpirole administration on checking were assessed. Subsequently, the effects on checking of different behavioural challenges, including reward omission and the use of unpredictable reinforcement schedules, were tested. RESULTS: Prior autoshaping increased checking. Sign-trackers and goal-trackers responded differently to quinpirole sensitization, reward omission and reinforcement uncertainty. Sign-trackers showed greater elevations in dysfunctional checking, particularly during uncertainty. By contrast, goal-trackers predominantly increased functional checking responses, possibly in response to reduced discrimination accuracy in the absence of cues signalling which lever was currently active. CONCLUSIONS: The results are discussed in terms of how pavlovian associations influence behaviour that becomes compulsive in OCD and how this may be dependent on striatal dopamine D2 receptors.

Drink, drugs and disruption: memory manipulation for the treatment of addiction.

Addiction is a complex disorder, and one characterised by the acquisition of maladaptive instrumental (drug-seeking and drug-taking) and pavlovian (cue-drug associations) memories. These memories markedly contribute to the long-term risk of relapse, so reduction of the impact of these memories on behaviour could potentially be an important addition to current therapies for addiction. Memory reconsolidation may provide such a target for disrupting well-consolidated pavlovian cue-drug memories following an extensive drug history. Reconsolidation can be disrupted either by administering amnestic drugs in conjunction with a memory reactivation session, or by updating the memory adaptively through the induction of 'superextinction'. More work is needed before these therapies are ready for translation to the clinic, but if found clinically effective memory manipulation promises a radical new way of treating addiction.

Dissociation of hemi-spatial and hemi-motor impairments in a unilateral primate model of Parkinson's disease.

Monkeys with unilateral lesions of nigrostriatal dopamine projections were tested on a series of spatial tasks. One task, in which monkeys were required to use one or the other arm to retrieve food rewards from different positions, allowed separate assessment of the use of each arm in each hemi-space in order to distinguish hemi-spatial and hemi-motor impairments. The lesioned monkeys exhibited a persistent neglect of contralesional space when using either arm which could be dissociated from a motor impairment in the contralesional arm alone. Another task allowed free use of either arm across peri-personal space and demonstrated an ipsilesional bias in the monkeys' self-determined attention (orientation) to a task which they were trying to perform. It is argued that the tendency for monkeys with this lesion to rotate ipsilesionally is due to an ipsilesional deviation of the 'centre of interest' (determined by telencephalic circuitry) relative to 'straight ahead' (determined by brainstem circuitry). The dopamine projections may contribute to cortico-subcortical circuits which determine the spatial layout of mental representation, attention and intention. The results in this primate model of unilateral Parkinson's disease (PD) support the view that patients with left-sided Parkinsonian symptoms exhibit a unilateral deficit in spatial mental representation as well as their well-recognised motor symptoms. Patients with bilateral Parkinson's symptoms may exhibit bilateral deficits in mental representation.