Research report Interhemispheric involvement of the anterior cortical nuclei of the amygdala in rewarding brain stimulation Maı ¨a Miguelez, Amanda C. Kentner, Kim Deslauriers, Matthew Parkinson, George Fouriezos, Catherine Bielajew * School of Psychology, University of Ottawa, Ottawa, ON, Canada K1N 6N5 Accepted 28 December 2003 Abstract The amygdaloid complex is one of the structures thought to modulate brain stimulation reward (BSR) elicited from the median forebrain bundle (MFB). Previous metabolic and behavioral data from our laboratory point to the amygdaloid cortical nuclei as key to this process. In this study, thresholds for rewarding stimulation of the MFB were determined for 42 days, 21 days following an electrolytic lesion to amygdaloid nuclei ipsilateral to the stimulation electrode, and 21 days following one applied to the contralateral amygdala. A subset of animals showed post-lesion changes in MFB frequency thresholds that were maintained if not augmented after the second lesion. These ranged from 26% to 150% compared to baseline values, among the largest ever reported to our knowledge. Interestingly, damage to anterior sites within the cortical nuclei was the most effective in producing modifications to the rewarding value of the stimulation. Equally singular was the finding that contralateral lesions tended to alter thresholds more than ipsilateral ones, confirming our earlier finding of interhemispheric connectivity in amygdaloid modulation of MFB reward signals. This interpretation was substantiated by tracking long-term metabolic activity in the amygdala using cytochrome oxidase histochemistry. The density of reaction product at damaged amygdala sites was negatively correlated (r = À 0.90) with the increases in thresholds obtained at contralateral MFB loci. Together with the fact that such large lesion effects are seldom obtained, our metabolic results point to the existence of a relationship between these nuclei and reward signals generated at the MFB. Moreover, our data suggest that this communication takes place interhemispherically. D 2004 Elsevier B.V. All rights reserved. Keywords: Motivation and emotion; Brain stimulation reward; Anterior cortical amygdala; Median forebrain bundle; Electrolytic lesion; Cytochrome oxidase 1. Introduction The median forebrain bundle (MFB) is made up of as many as 50 fiber collections of different lengths, origins, and destinations [41,63]. Because of the ease with which brain stimulation reward (BSR) can be elicited from it, this bundle has become a major focus for the study of the neural circuitry underlying goal-oriented behaviours (see Stellar and Stellar [57]). Although structures that are part of the MFB have been at the heart of the majority of BSR investigations, some loci located outside of this bundle are known to modulate BSR elicited from the MFB (see, for example, Ref. [7]) [55,61]. Among these sites, the amygdala (also called amygdaloid complex) is of primary interest due to its anatomical and functional characteristics. First, the idea that the amygdaloid complex may modulate MFB reward has anatomical valid- ity; the stria terminalis and the ventral amygdalofugal pathway—two major fiber systems—link the two areas [18,48]. Second, many converging lines of evidence clearly implicate the amygdaloid complex in motivation and emo- tion (see Refs. [49,10]). A wide variety of behaviours, ranging from feeding [27,28,42] and sex [29] to the medi- ation of sensory associative learning [15,69] has been linked with amygdaloid activity. Recent evidence also points at parts of the amygdaloid complex as determinant structures in the processes underlying drug reinforcement and addic- tion [31–33], and some amygdaloid nuclei have been shown to support BSR [25,43,60]. In addition, stimulation of rewarding MFB sites has been associated with an increase in cellular activity as measured by the c-Fos 0006-8993/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2003.12.033 * Corresponding author. +1-613-562-5800x4687; fax: +1-613-562- 5147. E-mail address: catch@uottawa.ca (C. Bielajew). www.elsevier.com/locate/brainres Brain Research 1003 (2004) 138 – 150