Compulsive use of dopamine replacement therapy: a model for stimulant drug addiction?

The compulsive use of dopamine replacement therapy (DRT) or dopamine dysregulation syndrome (DDS) is one of the behavioural disturbances reported in some patients with Parkinson's disease (PD) and other disorders who are receiving DRT. We draw this phenomenon to the attention of the addiction field as a topic deserving of more systematic study. We outline: the clinical features, epidemiology and clinical correlates of the disorder; the unresolved issues in its definition and diagnosis; and its potential relevance to neurobiological models of psychostimulant addiction. We argue that compulsive DRT use may provide a useful model for drug addiction, while advancing our understanding of the neurobiology of addiction and improving the management of PD patients with the disorder.

Impulse control disorders in patients with Parkinson's disease receiving dopamine replacement therapy: evidence and implications for the addictions field.

AIMS: To describe the prevalence, phenomenology and correlates of 'impulse control disorders' (ICDs) in patients with Parkinson's disease (PD) treated with dopamine replacement therapy (DRT); to assess the strength of the evidence that DRT plays a contributory causal role in these disorders; and to highlight the implications of these disorders for research in the addiction field. METHODS: PubMed and Web of Science databases were searched and the reference lists of papers examined. RESULTS: The prevalence of ICDs in Parkinson's patients using DRT varied between 3.5% and 13.6%, depending on the severity and range of disorders assessed. PD patients with ICDs were: generally younger; had an earlier onset of PD; had a personal or family history of substance abuse or an ICD; and were more likely to be treated with dopamine receptor agonists (DA agonists) than levodopa (l-dopa). There is reasonable evidence that dopaminergic medications play a causal role in ICDs in that they occur at a higher rate in an otherwise low-risk population of adults, begin after initiation of DA agonist therapy and cease upon its discontinuation. A causal relationship is biologically plausible, but the role of other factors (such as concurrent mood disorders) remain to be clarified by better-controlled studies. CONCLUSIONS: Impulse control disorders among patients with Parkinson's disease receiving dopamine replacement therapy may provide a unique opportunity for addiction researchers to study the neurobiology of impulsive forms of behaviour (such as problem gambling) that appear to be caused, in part, by the therapeutic use of dopamine receptor agonists.

The consequences of beer consumption in rats: acute anxiolytic and ataxic effects and withdrawal-induced anxiety.

RATIONALE: Rats avidly consume standard off-the-shelf beer; however, the behavioural consequences of beer consumption in rodents have hardly been studied. OBJECTIVES: The present study examined the acute anxiolytic and ataxic effects of beer consumption in rats and the anxiogenic effects of withdrawal from free access to beer. METHOD: In experiment 1, male Wistar rats received 30 min access to "near-beer" each day (a malt beverage that looks and tastes like beer but which contains <0.5% ethanol). On the test day, for some rats, ethanol (either 2% or 4% v/v) was added to the near-beer to make it resemble standard (ethanol-containing) beer of "light" (2.5% beer) or full strength (4.5% beer). Immediately after this, rats were tested on their response to a predatory cue (a fabric collar that had been worn by a cat) and on an accelerating rotarod. In experiment 2, rats were trained in the same drinking paradigm as above and then tested on a further battery of anxiety tests. In experiment 3, rats were given continuous home cage access to either 4.5% beer or near-beer for 35 days. Half of the rats were then denied access to beer or near-beer for 24 h and then tested on the same anxiety test battery as in experiment 2. RESULTS: Rats drinking 4.5% beer approached a predatory cue significantly more than those given near-beer, indicating an anxiolytic effect. In experiment 2, rats drinking 4.5% beer displayed less anxiety-like behaviour in the elevated plus maze and emergence tests but not in the social interaction test. Rats given 4.5% beer fell off the rotarod significantly faster than rats given near-beer, indicating an ataxic effect. Rats previously given 4.5% beer drank significantly less near-beer the following day, suggesting a moderate aversion the day after beer consumption. In experiment 3, rats denied access to 4.5% beer showed significantly less social interaction and took longer to emerge into an open field than controls. CONCLUSION: These results are the first to our knowledge to show that rats will consume beer at levels that produce clear effects on anxiety and on motor co-ordination, and that will eventually produce behavioural signs of withdrawal.

Not all 'predator odours' are equal: cat odour but not 2,4,5 trimethylthiazoline (TMT; fox odour) elicits specific defensive behaviours in rats.

The behavioural responses to two commonly used 'predator odours' were assessed in male Wistar rats. Cat odour was presented to rats in the form of a piece of collar that had been worn by a domestic cat. Fox odour was presented in an equivalent piece of (unworn) collar that had been impregnated with 2,4,5 Trimethylthiazoline (TMT)-an extract of fox faeces. Other rats were exposed to collars containing Triethylamine (TEA), a putrid fishy smell, or formaldehyde, which has an acrid irritating smell. Experiment 1 showed that rats approached cat odour, TMT and TEA significantly less than they did an unworn collar. However, only cat odour increased retreat to the hide box, reduced locomotor activity and elicited 'head out' behaviour. When tested immediately after odour exposure, only cat odour exposed rats showed increased anxiety in the elevated plus maze and suppressed activity in a 90-min general activity test. When returned to the odour-paired environment 24 h later in the absence of test odours, only rats that had previously received cat odour showed evidence of conditioned fear. Experiment 2 showed that rats given the benzodiazepine drug midazolam (0.5 mg/kg) display increased approach and decreased defensiveness towards a cat odour impregnated collar. In contrast, midazolam accentuated the avoidance of TMT and formaldehyde containing collars. Experiment 3 showed that when cat odour was presented in a small, enclosed environment, rats display increased body immobility, decreased grooming and increased orientation towards the odour-exuding stimulus. These responses were not seen with TMT or TEA containing collars. Taken together, these results suggest that while cat odour strongly elicits specific defensive behaviours in rats, TMT has effects that are more characteristic of an aversive odour. We suggest that the results of some previous studies using TMT may need to be reassessed.