Effects of Losartan Potassium on Central Dopaminergic System in Mice

Pandi, Vijaya; Naik, Anantha Nagappa; Thakurdesai, Prasad

doi:10.3923/jpt.2007.551.558

Cited by 3 publications

(2 citation statements)

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“…Recent work in humans reported increased reward-related processing by a single dose of losartan in the midbrain dopamine system (24,25). There is some evidence that the observed effects on the dopaminergic system are not due to losartan per se but instead arise due to its active metabolite (EXP 3174) (80), which should be considered by future work. Adding further to the discussion on potential underlying mechanistic pathways of the effects reported here, losartan has also been shown to reduce encoding of negative, but not positive, memories via reduced hippocampus-amygdala connectivity (18).…”

Section: Discussionmentioning

confidence: 91%

“…The task has previously been shown to provide reliable learning estimates via computational readouts (78), which was also supported by relatively high ICC scores in our sample. While similar approaches have been fruitful in understanding psychiatric conditions (79,80), recent work has also called for more naturalistic and ecologically valid paradigms (87).…”

Section: Discussionmentioning

confidence: 99%

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Reduction of aversive learning rates in Pavlovian conditioning by angiotensin II antagonist losartan: a randomised controlled trial

Zika¹,

Appel²,

Klinge³

et al. 2023

Preprint

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The angiotensin receptor blocker losartan has been linked to aspects of aversive learning such as fear acquisition and extinction, inhibition of aversive learning rates and reduced post-traumatic stress disorder (PTSD) symptoms. Here, we investigate the influence of losartan on aversive Pavlovian conditioning using a probabilistic learning paradigm. In a double-blind, randomized placebo-controlled design, we tested 45 healthy volunteers during a baseline session (session 1), after application of losartan or placebo (session 2) and during a follow-up session (session 3). On each session, participants engaged in a task where they had to predict the likelihood of an electrical stimulation on every trial while the true shock contingencies repeatedly switched between phases of high and low shock threat. Computational reinforcement learning models were used to investigate learning dynamics. Acute administration of losartan significantly reduced participants’ adjustment during both low-to-high and high-to-low threat changes. This was driven by reduced aversive learning rates on the drug session compared to baseline. The 50mg drug dose did not induce reduction of blood pressure or change in reaction times, ruling out general reduction in attention and engagement. Decreased adjustment of aversive expectations to low-to-high, but not high-to-low, threat change was maintained on a follow up session 24hrs later, suggesting a possible role of losartan in prevention of formation of aversive associations on longer time scales.

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