Amphetamine, past and present – a pharmacological and clinical perspective

“…The results indicated that amphetamine was a highly selective uptake blocker of DAT, while cocaine was a relatively non-selective uptake blocker, which is consistent with previous reports (Volkow et al, 2000). The method evaluation results also showed that amphetamine acted as a selective releaser at DAT, but was inactive at SERT, which is consistent with previous reports (Baumann et al, 2012; Heal et al, 2013; Simmler et al, 2013).…”

“…Our results demonstrate that a systemic manipulation can selectively change behavior and the underlying neural mechanisms. They support the hypothesis that the spatially selective behavioral and neuronal changes we observed involved an interaction between the diffuse activity of neurotransmitters at the level of top-down control areas (as suggested by in vitro and in vivo measurements of stimulant effects; for review, see Arnsten, 2006;Heal et al, 2013;Mueller et al, 2017) and the localized activity of neurotransmitters at the level of early sensory areas like V4 (as suggested by in vitro and in vivo studies of attention effects; Noudoost & Moore, 2011a; for review, see Deco & Thiele, 2009;Noudoost & Moore, 2011b;Schmitz & Duncan, 2018). While electrophysiological studies have differed in their findings regarding the role of prefrontal cortex in mediating the behavioral effects of methylphenidate (Devilbiss & Berridge, 2008;Gamo et al, 2010;Noudoost & Moore, 2011a;Rajala et al, 2020;Tremblay et al, 2019), the combined global and selective changes we observed here support that global processes can interact with frontoparietal networks (Engelmann et al, 2009;Padmala & Pessoa, 2011) through dopaminergic projections (Botvinick & Braver, 2015;Noudoost & Moore, 2011b) to enhance selective attention processing (Corbetta & Shulman, 2002;Kastner & Ungerleider, 2000;Moore & Zirnsak, 2017;Mueller et al, 2017).…”

“…The pharmacological validation study showed that the ActualHCA™ system was able to detect effects on ambulatory and vertical activities, and subcutaneous temperature for the test agents chlorpromazine, clonidine and amphetamine. The observed findings were consistent with the known pharmacology of these test agents in rats (Fog, 1970;Heal et al, 2013;Mattsson et al, 1996;Moscardo et al, 2007;Van der Laan & De Groot, 1988). Their effects on activity and temperature, as detected using the modified Irwin test and ActualHCA™ were in agreement, despite using different cohorts of animals in independent experiments.…”

“…The results indicated that amphetamine was a highly selective uptake blocker of DAT, while cocaine was a relatively non-selective uptake blocker, which is consistent with previous reports (Volkow et al, 2000). The method evaluation results also showed that amphetamine acted as a selective releaser at DAT, but was inactive at SERT, which is consistent with previous reports (Baumann et al, 2012; Heal et al, 2013; Simmler et al, 2013).…”

“…Our results demonstrate that a systemic manipulation can selectively change behavior and the underlying neural mechanisms. They support the hypothesis that the spatially selective behavioral and neuronal changes we observed involved an interaction between the diffuse activity of neurotransmitters at the level of top-down control areas (as suggested by in vitro and in vivo measurements of stimulant effects; for review, see Arnsten, 2006;Heal et al, 2013;Mueller et al, 2017) and the localized activity of neurotransmitters at the level of early sensory areas like V4 (as suggested by in vitro and in vivo studies of attention effects; Noudoost & Moore, 2011a; for review, see Deco & Thiele, 2009;Noudoost & Moore, 2011b;Schmitz & Duncan, 2018). While electrophysiological studies have differed in their findings regarding the role of prefrontal cortex in mediating the behavioral effects of methylphenidate (Devilbiss & Berridge, 2008;Gamo et al, 2010;Noudoost & Moore, 2011a;Rajala et al, 2020;Tremblay et al, 2019), the combined global and selective changes we observed here support that global processes can interact with frontoparietal networks (Engelmann et al, 2009;Padmala & Pessoa, 2011) through dopaminergic projections (Botvinick & Braver, 2015;Noudoost & Moore, 2011b) to enhance selective attention processing (Corbetta & Shulman, 2002;Kastner & Ungerleider, 2000;Moore & Zirnsak, 2017;Mueller et al, 2017).…”

“…The pharmacological validation study showed that the ActualHCA™ system was able to detect effects on ambulatory and vertical activities, and subcutaneous temperature for the test agents chlorpromazine, clonidine and amphetamine. The observed findings were consistent with the known pharmacology of these test agents in rats (Fog, 1970;Heal et al, 2013;Mattsson et al, 1996;Moscardo et al, 2007;Van der Laan & De Groot, 1988). Their effects on activity and temperature, as detected using the modified Irwin test and ActualHCA™ were in agreement, despite using different cohorts of animals in independent experiments.…”

“…The results indicated that amphetamine was a highly selective uptake blocker of DAT, while cocaine was a relatively non-selective uptake blocker, which is consistent with previous reports (Volkow et al, 2000). The method evaluation results also showed that amphetamine acted as a selective releaser at DAT, but was inactive at SERT, which is consistent with previous reports (Baumann et al, 2012; Heal et al, 2013; Simmler et al, 2013).…”

“…Our results demonstrate that a systemic manipulation can selectively change behavior and the underlying neural mechanisms. They support the hypothesis that the spatially selective behavioral and neuronal changes we observed involved an interaction between the diffuse activity of neurotransmitters at the level of top-down control areas (as suggested by in vitro and in vivo measurements of stimulant effects; for review, see Arnsten, 2006;Heal et al, 2013;Mueller et al, 2017) and the localized activity of neurotransmitters at the level of early sensory areas like V4 (as suggested by in vitro and in vivo studies of attention effects; Noudoost & Moore, 2011a; for review, see Deco & Thiele, 2009;Noudoost & Moore, 2011b;Schmitz & Duncan, 2018). While electrophysiological studies have differed in their findings regarding the role of prefrontal cortex in mediating the behavioral effects of methylphenidate (Devilbiss & Berridge, 2008;Gamo et al, 2010;Noudoost & Moore, 2011a;Rajala et al, 2020;Tremblay et al, 2019), the combined global and selective changes we observed here support that global processes can interact with frontoparietal networks (Engelmann et al, 2009;Padmala & Pessoa, 2011) through dopaminergic projections (Botvinick & Braver, 2015;Noudoost & Moore, 2011b) to enhance selective attention processing (Corbetta & Shulman, 2002;Kastner & Ungerleider, 2000;Moore & Zirnsak, 2017;Mueller et al, 2017).…”

“…The pharmacological validation study showed that the ActualHCA™ system was able to detect effects on ambulatory and vertical activities, and subcutaneous temperature for the test agents chlorpromazine, clonidine and amphetamine. The observed findings were consistent with the known pharmacology of these test agents in rats (Fog, 1970;Heal et al, 2013;Mattsson et al, 1996;Moscardo et al, 2007;Van der Laan & De Groot, 1988). Their effects on activity and temperature, as detected using the modified Irwin test and ActualHCA™ were in agreement, despite using different cohorts of animals in independent experiments.…”