Serotonin-receptor Agonism in Reward Processing

University of Oxford63 enrolled

Overview

There is growing animal and human evidence for role of 5HT1A receptor agonism in treating depression and reward deficits. The next step is to translate this evidence directly into humans by characterising the effects of buspirone, as a 5HT1A agonist, on cognitive models of reward and emotional processing. There is a paucity of behavioural evidence for the effect of 5HT1A receptor agonism, using buspirone as a probe, on primary reward processing (e.g. food), effort-based decision making or reward learning. Furthermore, the effects of 5HT1A agonism on non-emotive cognition, such as working memory, has yet to be investigated at a behavioural level in humans. This study will characterise the effects of buspirone, as a probe for 5HT1A receptor agonism, on reward processing in human cognitive models. Furthermore it will examine its role in emotional processing and working memory. This will add to the evidence base of the neurocognitive effects of 5HT1A receptor agonism in humans, which is of relevance to the development of this as a target for future treatment development. The study will be a double blinded, placebo controlled study involving healthy volunteers. Participants will receive a single dose of buspirone and then undergo a battery of psychometric testing to examine reward processing, emotional processing and a memory. Frequent monitoring of temperature and salivary cortisol shall be taken as surrogate markers of pre- and postsynaptic 5HT1A receptor activation.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Enrollment

Conditions

Anhedonia

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Participant is willing and able to give informed consent for participation in the research * Male or female * Body mass index in the range of 18 to 30 * Not currently taking any medications (except for contraception) Exclusion Criteria: * • Any current Axis 1 The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) psychiatric disorder * Any previous episode of a severe mental illness, * A first degree relative diagnosed with Bipolar Affective Disorder Type 1 or Schizophrenia * Body Mass Index outside the range of 18 to 30 inclusive * Any significant current medical condition likely to interfere with conduct of the study or analysis of data (epilepsy, renal disease, hepatic disease, myasthenia gravis, acute closed-angle glaucoma) * Current use of psychoactive and / or medically significant medication as judged by a study medic, whether prescribed or bought over the counter (the contraceptive pill, the Depo-Provera injection or the progesterone implant will not result in exclusion) * Past history of dependence to illicit substances, and any consumption of illicit substances in the three months prior to the study * Currently pregnant or breast feeding * Known lactase deficiency or any other problem absorbing lactose, galactose, or glucose * Participation in a study using the same tasks in the last year * Any physical (including visual and auditory) or language impairment that would make complying with the study protocol challenging. This includes any taste/olfactory disturbance e.g. secondary to Covid-19 infection

Outcomes

Primary Outcomes

Primary reward perception

Visual Analogue Scale of anticipation of pleasure, intensity of taste and pleasure experienced when tasting one of four 4 tastes representing a primary reward stimulus processing.

Time frame: On day of intervention (30 minutes pre-intervention and post-intervention (60 - 180 minutes))

Effort based reward task:

offer acceptance based upon effort required (grip force on hand held dynamometer) to obtain outcome and success rate in expending correct amount of effort required for reward

Time frame: On day of intervention ( 90 - 180 minutes post intervention)

Changes in reward sensitivity

Sensitivity to reward as measured by the Probabilistic Instrumental Learning Task (Amount won, amount lost, total monetary amount earned , proportion of participants choosing the correct symbol in win and loss trials)