Enhanced Taste Recognition Following Subacute Treatment With The Dopamine D2/D3 Receptor Agonist Pramipexole in Healthy Volunteers

Abstract

Background Patients with Parkinson’s disease (PD) show impaired performance in taste recognition tests, which suggests a possible dopaminergic influence on gustatory functioning. To experimentally test this hypothesis, we assessed whether pharmacological manipulation of dopaminergic signalling in healthy volunteers can affect performance in a standardised taste recognition test. Methods Physically and mentally healthy volunteers (n = 40, age 18 to 43 years) were randomly allocated to treatment with either pramipexole or placebo using a double-blind, parallel-group design. After 12 to 15 days of treatment (dose titrated up from 0.25 mg/day of pramipexole salt to 1.0 mg/day), taste recognition performance was assessed using a standardised and validated assay (taste strip test). Additionally, visual analogue scale ratings of subjective pleasantness and disgustingness of taste samples were obtained. Results Compared to the placebo group, participants receiving pramipexole showed significantly higher total recognition accuracy (MedianPramipexole = 14.0, MedianPlacebo = 13.0, U = 264.5, p = 0.04). This was driven by a higher sensitivity for taste in the pramipexole group. Exploratory analysis of pleasantness and disgustingness ratings of appetitive (sweet) versus aversive (bitter) stimuli suggested that pramipexole treatment was associated with overall blunted hedonic responses, but this effect did not survive the inclusion of nausea (a side effect of treatment) as a covariate in the analysis. Conclusions Healthy volunteers who received subacute pramipexole treatment exhibited higher taste recognition performance in comparison to a placebo group. This finding is consistent with a proposed role of the dopaminergic system in gustatory functioning and could have important theoretical and clinical implications.

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“…Participants attended a screening visit where their eligibility was assessed by a medical doctor (DH or AK) prior to their inclusion in the study. The screening visit consisted of an explanation of study procedures, collection of written informed consent, completion of the Structured Clinical Interview of the DSM-5 (SCID-5, First et al 2015 ) and Beck’s Depression Inventory (Beck et al 1996 ) to rule out psychiatric conditions and depression, and other questionnaires and behavioural tasks not reported here as part of a wider research programme which was pre-registered at https://clinicaltrials.gov/ct2/show/NCT03681509 (For other published studies from the programme, see Martens et al 2021 ; Halahakoon et al 2022 ; Kaltenboeck et al 2022 ). The maximum duration of time allowed between screening and inclusion in the study was 28 days.…”

Editorial Perspective: Bridging the translational neuroscience gap in autism – development of the ‘shiftability’ paradigm

“…In another category, the goal is to investigate neuropsychopharmacology in so‐called ‘healthy volunteers’, and then to infer what the results may mean for people with a neuropsychiatric condition. For example, using pramipexol to understand dopaminergic control of gustatory experiences relevant to Parkinson's disease (Kaltenboeck, Halahakoon, Harmer, Cowen, & Browning, 2022) or using arbaclofen and clobazam to understand the control of sensory inhibition in neurotypical people to gain insight into sensory features of autism (Mentch, Spiegel, Ricciardi, & Robertson, 2019). These designs have produced useful insights into a range of neurological and psychiatric conditions, however, they usually involve either cases or controls.…”