, Volume 231, Issue 5, pp 825–840 | Cite as

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

  • Kristine L. Keller
  • Fiori R. Vollrath-Smith
  • Mehrnoosh Jafari
  • Satoshi IkemotoEmail author
Original Investigation



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


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.


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.


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.


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.


Dietary restriction Incentive motivation Manic–depressive illness Visual sensation Drug abuse Amphetamine Lithium 



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.

Financial Disclosures

The authors have no financial disclosure to make.


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Copyright information

© Springer-Verlag Berlin Heidelberg (outside the USA) 2013

Authors and Affiliations

  • Kristine L. Keller
    • 1
  • Fiori R. Vollrath-Smith
    • 1
  • Mehrnoosh Jafari
    • 2
  • Satoshi Ikemoto
    • 1
    Email author
  1. 1.Behavioral Neuroscience Research Branch, National Institute on Drug Abuse, National Institutes of HealthU.S. Department of Health and Human ServicesBaltimoreUSA
  2. 2.Graduate School of Systemic NeurosciencesLudwig Maximilian UniversityMunichGermany

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