The effects of the prodrug Vyvanse on spatial working memory and adiposity in rats
Abstract
The present study investigated the influence of Vyvanse (lisdexamfetamine), a psychomotor stimulant, on spatial working memory, body weight, and adiposity in rats. Control and experimental rats were placed in individual cages equipped with a running wheel, and food and water were provided ad-libitum. The study was divided into three periods: 1) habituation, 2) experimental, and 3) withdrawal. Control rats received a placebo in periods 1, 2 and 3, while experimental rats received a placebo in periods 1 and 3. Experimental rats received a treatment of Vyvanse in place of the placebo during period 2. Spatial working memory was examined by utilizing the methodology of the Morris Water Maze. Rats were evaluated by performance in the maze each day during the experimental and withdrawal periods. Each assessment consisted of two trials. The first was a sample trial in which an escape platform was discovered by trial and error. The second was a test trial in which the platform location was recalled using working memory. Platform placement and start location of the rats were changed every session. It was hypothesized that Vyvanse would effectively enhance spatial working memory, and significantly decrease body weight and adiposity without side effects on activity level and anxiety in rats. Results supported the hypothesis. Compared to control rats, Vyvanse treated rats had significant improvement in working memory and significantly lowered body weight, as well as significantly decrease…
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Only one study has reported that chronic lisdexamfetamine treatment effectively enhanced spatial working memory in the Morris water maze.
“To our knowledge, only one study has reported that chronic lisdexamfetamine treatment effectively enhanced spatial working memory in the Morris water maze (15)”
LDX modulates seven human protein targets: it activates TAAR1 and inhibits SLC18A2, DAT, NET, SERT, MAOA, and MAOB.
“LDX has been reported to modulate with pharmacological action of seven human protein targets (Table 2). On the one hand, it acts as activator of TAAR1. On the other hand, six protein targets are inhibited by LDX: synaptic vesicular amine transporter (SLC18A2), DAT (SLC6A3), NET (SLC6A2), SERT (SLC6A4) and amine oxidase [flavin-containing] (MAO) A and B [153–157].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [155]
LDX induces activation of dopaminergic and adrenergic receptors DRD1, DRD5, DRD2, ADRA2A, ADRA2B and ADRA2C, contributing to neurotransmission signalling.
“First, LDX induces activation of the known dopaminergic and adrenergic receptors DA receptor 1A (DRD1), DA receptor 1B (DRD5), DRD2, ADRA2A, ADRA2B and alpha-2C adrenergic receptor (ADRA2C) [155, 158, 159], contributing to neurotransmission signalling.”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [155]
All of these targets are involved in presynaptic signalling, and LDX therefore has a role in regulating three main NT pathways: DA, NE and serotonin.
“All of these targets are involved in the presynaptic signalling, and LDX therefore has a role in regulating three main NT pathways: DA, NE and serotonin.”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [155]
The modulation of LDX involves dopaminergic and adrenergic neurotransmission, inducing upregulation of ADRA2A, ADRA2B, ADRA2C, DRD1 and DRD5, and immunomodulation by modulating several interleukins, mainly IL-4 and IL-10 that present an anti-inflammatory profile.
“The modulation of LDX involves dopaminergic and adrenergic neurotransmission, inducing upregulation of ADRA2A, ADRA2B, ADRA2C, DRD1 and DRD5 [155, 158, 159], and immunomodulation by modulating several interleukins, mainly IL-4 and IL-10 that present an anti-inflammatory profile [160].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [155]
LDX amplifies dopaminergic transmission in the mesolimbic and mesocortical tracts.
“LDX amplifies dopaminergic transmission in the mesolimbic and mesocortical tracts (two major pathways in cognition and memory) [155].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [155]
DRD1, DRD5, ADRA2A, ADRA2B and ADRA2C are activated downstream by LDX.
“The DRD1, DRD5, ADRA2A, ADRA2B and ADRA2C are activated downstream by LDX [155, 158, 159].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [155]
LDX can promote the increase of DA in the synaptic cleft by activating TAAR1, which produces the efflux of monoamine NTs, mainly DA, from storage sites on presynaptic neurons.
“LDX can also promote the increase of DA in the synaptic cleft by activating protein TAAR1, which produces the efflux of monoamine NTs, mainly DA, from storage sites on presynaptic neurons [155, 177].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [155]
Cites
Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine
Pennick (2010) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s9749 · Cited by 170 · see citing works
The Cognition-Enhancing Effects of Psychostimulants Involve Direct Action in the Prefrontal Cortex
Spencer, R. C., Devilbiss, D. M., & Berridge, C. W. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.09.013 · Cited by 164 · see citing works
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Quintero, J., Gutiérrez-Casares, J. R., & Álamo, C. (2022) · Neurology and Therapy · doi:10.1007/s40120-022-00392-2 · Cited by 70 · see citing works
“Regulation of Postsynaptic Receptors LDX amplifies dopaminergic transmission in the mesolimbic and mesocortical tracts (two major pathways in cognition and memory) [155].”
BackgroundInfluentialJian-min, C., Zhi-yuan, W., Shi-xuan, W., Rui, S., Ning, W., & Jin, L. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.885574 · Cited by 7 · see citing works
“To our knowledge, only one study has reported that chronic lisdexamfetamine treatment effectively enhanced spatial working memory in the Morris water maze (15), which is consistence to our results.”
BackgroundResult
- Authors
- Ekstrand, E., Murphy, H. M., & Wideman, C. H.
- Affiliations
- John Carroll University (US)
- Corresponding author
- Ekstrand, Ethan
- Venue
- Pharmacology Biochemistry and Behavior
- Publisher
- Elsevier BV
- Published
- 2019-11
- Volume
- 186
- Pages
- 172765
- ISSN
- 0091-3057 (ISSN-L)
- OpenAlex
- W2970018156
- Cited by
- 12
- References
- 2
- Citations by year
- 2026: 2 · 2025: 3 · 2023: 3 · 2022: 2 · 2021: 2
- FWCI
- 0.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacology Biochemistry and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Funders
- John Carroll University
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- Vyvanse, lisdexamfetamine, prodrugs, spatial working memory, adiposity, body weight, psychostimulants, Morris water maze, wheel running, anxiety, dietary intake
- MeSH terms
- Lisdexamfetamine Dimesylate, Central Nervous System Stimulants, Animals, Body Weight, Memory, Short-Term, Prodrugs, Maze Learning, Adiposity, Rats
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