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Updated: May 7, 2026
A Procedure to Study the Effect of Prolonged Food Restriction on Heroin Seeking in Abstinent Rats
Published on: November 11, 2013
Synergistic interaction between caloric restriction and amphetamine in food-unrelated approach behavior of rats
Kristine L Keller1, Fiori R Vollrath-Smith, Mehrnoosh Jafari
1Behavioral 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.
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.
