Investigation of KB-128 on Methamphetamine-Induced Hyperactivity

Project: Research project

Project Details

Description

ATTACHMENT A: Scope of Work

Investigation of KB-128 on Methamphetamlne-lnduced Hyperactivity

Hypothesis: We hypothesize the mixed 5-HT2cR agonist/5-HT2AR antagonist, KB-128, will reduce methamphetam1ne-induced hyperactivity. This rationale Is based on a multitude of publications from the Cunningham laboratory and others that show adm1nistrat1on of2cR agonist or 5-HT2AR antagonist alone or In combination reduces psychost1mulant-evoked hyperact1vIty in rats (Mao et al., 2022 PMID: 35430417: McMahon et al., 2001 PMID11259563: Filip et al., 2003 PMID12721337: Filip et al., 2004 PMID15131246: Pokros et al., 2012 PMC3476845: Soto et al, 2018 PMC5862780).

Experimental Overview: Male, Sprague-Dawley rats (N=32/n=8 per treatment) will acclimate to UTMB facilities for one week prior to pharmacological testing and behavioral assessments. Rats will habituate to the testing environment for 1.5h/day for three days prior to the start of the experiment. Animals will be divided into four treatment groups (methamphetamine [METH) + vehicle or KB-128 (5, 10 , 20 mg/kg); i.p.). On the test day, rats will receive the assigned treatment and be immediately placed into the locomotor activity chambers for 15 min to assess impact of KB-128 on basal motor behavior. After basal activity is recorded, rats will be briefly removed from activity chambers for treatment with methamphetamine (1 mg/kg; i.p.) and placed back into activity chambers for 75 min to determine effect of KB-128 on METH-evoked hyperactivity. This dose of METH was informed by multiple publications demonstrating stimulatory effects on locomotor activity in male Sprague-Dawley rats (Wiah et al., 2022 PMC9850846; Gentry et al., 2004 PMID: 15582684; Hikichi 2015 PMID: 25837934).

Power Analysis: To achieve statistical significance with a moderate-large effect size with power of 0.8 and a = 0.05, n=8/dose will assure the study is sufficiently powered.

StatusFinished
Effective start/end date3/15/246/15/24

Funding

  • Kuleon, LLC ( Award # ): $9,313.00

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