Addiction and Dose Response: The Psychomotor Stimulant Theory of Addiction Reveals That Hormetic Dose Responses Are Dominant

Abstract

In 1987 Wise and Bozarth proposed a psychomotor stimulant theory of addiction whose most consistent feature was enhanced forward (horizontal) locomotion. While controversial, the theory of Wise and Bozarth has had substantial impact on addiction behavior theory over the past two decades, being cited over 1,400 times. The present assessment places the theoretical formulation of Wise and Bozarth (1987) within a dose-response framework. This analysis demonstrates that the psychomotor stimulant effects of addictive drugs routinely display biphasic dose-response relationships that are consistent with the quantitative features of the hormetic dose-response model. This is the case, regardless of addictive agent, animal model, and experimental protocol employed. Not only do these findings suggest an important role for the hormetic dose response model in the assessment of addictive behaviors, they also further extend the generalizability of the hormesis dose-response model concept within the biomedical sciences.

Cellular Stress Responses, The Hormesis Paradigm, and Vitagenes: Novel Targets for Therapeutic Intervention in Neurodegenerative Disorders

“…Failure to accurately predict the effects of drugs and chemicals can lead to failed clinical trials, inadequate patient care, and potentially harmful governmental regulations (40,73,135,143). While traditional dose-response models have failed to accurately predict responses in the low-dose zone in large-scale studies, the hormetic dose response performed extremely well, lending considerable support to other studies (56,57,65,66,(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)92) that have suggested that the process of drug development and chemical hazard=risk assessment could be improved in significant ways by a consideration of the hormetic dose response in the design, execution, and analysis of toxicological and pharmacological investigations. Consequently, this article will introduce the hormetic dose-response concept, including its scientific foundations, toxicological and pharmacological implications, and its applications to the field of neuroprotection and their mechanistic foundations.…”

Effects of synthetic cathinones contained in “bath salts” on motor behavior and a functional observational battery in mice

“…A defining behavioral characteristic of psychomotor stimulants is their propensity to increase locomotion in rodents, an effect that is strongly associated with their high addiction potential (Calabrese, 2008; Wise and Bozarth, 1987). All synthetic cathinones tested in the present study shared this effect, with different cathinones showing different potencies, magnitudes of stimulation, and durations of action.…”

“…This preference for drugs with quick onsets and shorter durations of action suggests that drugs with this profile are more likely to be abused. Therefore, of the cathinone analogs studied here, MDPV, mephedrone, and 4-FMC are likely to be most favored because they caused large, rapid initial increases in locomotor activity which deteriorated throughout the session (Calabrese, 2008; Fischman, 1989; Wise and Bozarth, 1987), albeit stimulants with rapid onset and slow offset (such as methamphetamine) may also be abused.…”

Prediction and Prevention of Prescription Drug Abuse: Role of Preclinical Assessment of Substance Abuse Liability

“…For example, a defining behavioral characteristic of psychomotor stimulants is their propensity to increase locomotion in rodents, an effect that is strongly associated with their high addiction potential (Calabrese, 2008; Wise & Bozarth, 1987). Amphetamine and other psychomotor stimulants dose-dependently increase locomotion and, at higher doses, may induce stereotypy, or repetitive movements (see methamphetamine results in Figure 2; Balster & Chait, 1978; French & Witkin, 1993).…”