Environmental Novelty Differentially Affects c-fosmRNA Expression Induced by Amphetamine or Cocaine in Subregions of the Bed Nucleus of the Stria Terminalis and Amygdala

Abstract

The environmental context in which amphetamine or cocaine are administered modulates both their acute psychomotor activating effects and their ability to induce sensitization. Here we report that environmental context differentially affects patterns of amphetamine- and cocaine-induced c-fosmRNA expression in the bed nucleus of the stria terminalis (BST) and amygdala of male rats.In the medial amygdala and medial posterior BST, exposure to novelty resulted in a marked increase in c-fosmRNA. Amphetamine given at home did not induce c-fosmRNA, and when given in the novel environment, did not increase levels beyond that observed for novelty alone. In the basolateral and lateral amygdala, amphetamine or cocaine at home or exposure to novelty induced c-fosmRNA. When amphetamine or cocaine was given in a novel environment the c-fosmRNA response was significantly enhanced. In the central nucleus of the amygdala (CEA) and oval subnucleus of the BST (BSTov), amphetamine administration at home produced a robust increase in c-fosmRNA expression, whereas exposure to novelty had little effect. In contrast to other brain regions examined, the c-fosmRNA response to amphetamine in a novel versus home environment was significantly smaller. In both “home” and “novel” amphetamine groups, c-fosmRNA in the BSTov and CEA was predominantly expressed in enkephalin-containing cells; coexpression with corticotropin-releasing hormone was rare.These data suggest that the context in which psychostimulants are given powerfully and differentially alters the response of limbic structures that have been functionally implicated in drug reinforcement and emotional behaviors.

Anxiolytic Activity of the MGLU2/3 Receptor Agonist LY354740 on the Elevated Plus Maze is Associated with the Suppression of Stress-Induced c-Fos in the Hippocampus and Increases in c-Fos Induction in Several Other Stress-Sensitive Brain Regions

“…Since LY354740 produced a c-Fos induction pattern in the amygdala similar to benzodiazepines, a similar mechanism could underlie the anxiolytic actions of LY354740. Furthermore, this model of reduced inhibitory tone is supported by an observation that amphetamine-induced c-Fos expression in the inhibitory neurons of the CeL was significantly greater in the home compared to the novel environment, suggesting that the activity of GABAergic neurons is indeed suppressed by a more stressful environment (Day et al, 2001). Further studies are needed to compare the level of c-Fos induction by LY35470 in the home vs a more aversive environment and to identify the neuronal populations activated by LY354740.…”

“…In addition to anxiolytic agents, c-Fos expression is induced in the CeL by different types of pharmacological agents, including anxiogenic compounds (Bittencourt and Sawchenko, 2000;Singewald and Sharp, 2000;Day et al, 2001), severe stress (Chowdhury et al, 2000), and peripheral autonomic challenges (McKitrick et al, 1992;Sagar et al, 1995). Clearly, c-Fos induction in the CeL is not specific for anxiolytic agents.…”

The effect of age on the dynamics and the level of c-Fos activation in response to acute restraint in Lewis rats

“…While the small activation rate of central amygdala at 1-2 h after stress had been reported before in young animals subjected to restraint [3,11,12,23], our study is to the best of our knowledge the first one to show that this effect could be altered by age. Further studies are needed in order to elucidate whether this is due to an impairment of inhibitory action of lateral part of central amygdala or oval nucleus of bed nucleus of the stria terminalis as suggested by Day et al [10,11].…”

Subthalamic Nucleus Lesions Enhance the Psychomotor-Activating, Incentive Motivational, and Neurobiological Effects of Cocaine

“…Pixels were counted when the optical density values were at least 3.5 SDs above background value (obtained from corpus callosum). Thus, the data are represented as relative integrated density in arbitrary units, which reflects both signal intensity and the number of pixels above background divided by total area (Badiani et al, 1998;Day et al, 2001;Uslaner et al, 2001b).…”