Brain Research 920 (2001) 106–116 www.elsevier.com / locate / bres Research report Environmental context modulates the ability of cocaine and amphetamine to induce c-fos mRNA expression in the neocortex, caudate nucleus, and nucleus accumbens a 1 1 b b Jason Uslaner , Aldo Badiani , Heidi E.W. Day , Stanley J. Watson , Huda Akil , a, * Terry E. Robinson a Biopsychology Programs, Department of Psychology, University of Michigan, East Hall, 525 East University Street, Ann Arbor, MI 48019-1109, USA b Mental Health Research Institute and Department of Psychiatry, University of Michigan, Ann Arbor, MI 48019-1109, USA Accepted 17 August 2001 Abstract We reported previously that environmental novelty enhances the acute psychomotor activating effects of amphetamine, its ability to induce behavioral sensitization, and its ability to induce c-fos mRNA in the striatum and other structures, relative to when amphetamine is given in the home cage. The purpose of the present experiment was 2-fold: to determine (1) whether environmental novelty has a similar effect on the ability of cocaine to induce c-fos mRNA, and (2) whether this effect is seen in neurologically-intact rats (in previous experiments we studied the intact hemisphere of rats with a unilateral 6-OHDA lesion). In the dorsal portion of the caudate putamen, core and shell of the nucleus accumbens, and in several cortical regions, both amphetamine (1.5 mg / kg) and cocaine (15 mg / kg) induced higher levels of c-fos mRNA expression when administered in a novel environment, relative to when they were administered in the home cage. The ability of environmental context to modulate psychostimulant drug-induced immediate early gene expression may be related to its ability to modulate forms of drug experience-dependent plasticity, such as behavioral sensitization.  2001 Elsevier Science B.V. All rights reserved. Theme: Neural basis of behavior Topic: Drugs of abuse: amphetamine and other stimulants Keywords: Immediate-early gene; C-fos; Psychostimulant; Amphetamine; Cocaine; Environment 1. Introduction induce neurobehavioral plasticity, are powerfully modu- lated by the context in which they are experienced. For Drugs of abuse produce a wide range of behavioral and example, using a simple animal model we have found that subjective effects, and with repeated administration they the acute psychomotor activating effects of amphetamine induce a number of neuroadaptive processes, including [7] and the ability of amphetamine, cocaine, or morphine tolerance, sensitization, dependence and addiction. How- to induce behavioral sensitization [2,5,8,9], are greatly ever, the acute effects of these drugs and their ability to enhanced when a drug is given in a distinct and relatively novel environment, relative to when it is given in a physically identical cage in which the animals live (i.e., at *Corresponding author. Tel.: 11-734-763-4361; fax: 11-734-763- ‘home’). 7480. In exploring the neurobiological mechanisms by which E-mail address: ter@umich.edu (T.E. Robinson). environmental context modulates the effects of amphet- 1 AB is now at the Department of Human Physiology and Pharmacology amine, we found that amphetamine-induced expression of ‘Vittorio Erspamer’, University of Rome ‘La Sapienza’, Rome, Italy, and the immediate early genes (IEGs) c-fos and arc is power- HEWD at the Department of Psychology, University of Colorado, Boulder (USA). fully modulated by environmental context [6,15]. Spe- 0006-8993 / 01 / $ – see front matter  2001 Elsevier Science B.V. All rights reserved. PII: S0006-8993(01)03040-2