Effects of benztropine analogs on delay discounting in rats
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ORIGINAL INVESTIGATION
Effects of benztropine analogs on delay discounting in rats Paul L. Soto 1
&
Takato Hiranita 2
Received: 28 December 2019 / Accepted: 31 August 2020 # This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020
Abstract Rationale Methylphenidate and d-amphetamine, medications used for treatment of attention deficit hyperactivity disorder (ADHD), are used recreationally and self-administered by laboratory animals. Benztropine (BZT) analogs, like those medications, increase synaptic dopamine levels but are less effective in maintaining self-administration, suggesting clinical utility with less abuse liability. Objectives The current study was designed to evaluate potential therapeutic effects of BZT analogs related to ADHD. Methods Rats responded under a delay-discounting procedure in which responses on one lever produced immediate delivery of a single food pellet and alternative responses produced four food pellets either immediately or with various temporal delays, with those delays arranged in ascending or random orders in different groups of rats. Selection of the smaller more immediate reinforcer has been suggested as an aspect of “impulsivity,” a trait with suggested involvement in ADHD. Other rats were studied under fixed-interval (FI) 300-s schedules to assess drug effects on behavior under temporal control. Results d-Amphetamine, methylphenidate, and the BZT analog AHN 1-055, but not AHN 2-005 or JHW 007, increased selection of the large, delayed reinforcer with either arrangement of delays. All drugs changed the temporal distribution of responses within the FI from one with responses concentrated at the end to a more uniform distribution. Changes in the temporal distribution of FI responding occurred with drugs that did not affect discounting suggesting that discounting does not arise directly from the same temporal control processes controlling FI responding. Conclusions AHN 1-055 may be of clinical utility in the treatment of ADHD. Keywords Benztropine analogs . Attention deficit hyperactivity disorder . Delay discounting . Fixed interval . Amphetamine . Methylphenidate . Rats . Operant . Food reinforcement
The psychostimulant drugs, methylphenidate and mixed damphetamine salts, are the standard medications used in the treatment of attention deficit hyperactivity disorder (ADHD) (Briars and Todd 2016). Methylphenidate is known to increase dopamine levels via blockade of dopamine uptake at presynaptic terminals (e.g., Schweri et al. 1985), whereas damphetamine releases dopamine from synaptic vesicles (e.g., Freyberg et al. 2016). Unfortunately, both methylphenidate and d-amphetamine can be abused (Clemow and Walker 2014), suggesting that drugs with lower potential for abuse
* Paul L. Soto [email protected] 1
Department of Psychology, Louisiana State University, Baton Rouge, LA 70803, USA
2
Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, USA
but that increase synaptic dop
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