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Synergistic interaction between caloric restriction and amphetamine in food-unrelated approach behavior of rats

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Abstract

Rationale

Approach behavior is regulated by the brain integrating information about environment and body state. Psychoactive drugs interact with this process.

Objectives

We examined the extent to which caloric (i.e., food) restriction, amphetamine (AMPH) and lithium interact in potentiating locomotor activity and responding reinforced by visual stimulus (VS), a reward unrelated to energy homeostasis.

Methods

Rats either had ad libitum access to food or received daily rations that maintained 85–90 % of their original body weights. Leverpressing turned on a cue light for 1 s and turned off house light for 5 s. AMPH and lithium were administered through intraperitoneal injections and diet, respectively.

Results

Food restriction or AMPH (1 mg/kg) alone had little effect on VS-reinforced responding; however, the combination of the two conditions markedly potentiated VS-reinforced responding (fourfold). Food restriction lasting 7 days or longer was needed to augment AMPH's effect on VS-reinforced responding. AMPH (0.3–3 mg/kg) potentiated locomotor activity similarly between food-restricted and ad libitum groups. Repeated injections of AMPH-sensitized locomotor activity, but not VS-reinforced responding. In addition, while chronic lithium treatments (0.2 % lithium carbonate chow) reduced VS-reinforced responding, chronic lithium further augmented AMPH-potentiated VS-reinforced responding.

Conclusions

Food restriction interacts with psychoactive drugs to potentiate goal-directed responding unrelated to food seeking in a much more powerful manner than previously thought. The novel finding that lithium can augment a psychostimulant effect of AMPH suggests caution when combining lithium and psychostimulant drugs in clinical settings.

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Acknowledgments

The present work was supported by the Intramural Research Program of National Institute on Drug Abuse, National Institutes of Health. The authors thank Ms. Amy N. Hamaker for conducting a pilot experiment and Dr. T. D. Gould for helping with lithium concentration analysis.

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The authors have no financial disclosure to make.

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Authors and Affiliations

  1. Behavioral Neuroscience Research Branch, National Institute on Drug Abuse, National Institutes of Health, U.S. Department of Health and Human Services, 251 Bayview Blvd., Suite 200, Baltimore, MD, 21224, USA

    Kristine L. Keller, Fiori R. Vollrath-Smith & Satoshi Ikemoto

  2. Graduate School of Systemic Neurosciences, Ludwig Maximilian University, Munich, Germany

    Mehrnoosh Jafari

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  1. Kristine L. Keller
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  2. Fiori R. Vollrath-Smith
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  3. Mehrnoosh Jafari
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  4. Satoshi Ikemoto
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Correspondence to Satoshi Ikemoto.

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Keller, K.L., Vollrath-Smith, F.R., Jafari, M. et al. Synergistic interaction between caloric restriction and amphetamine in food-unrelated approach behavior of rats. Psychopharmacology 231, 825–840 (2014). https://doi.org/10.1007/s00213-013-3300-9

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