Introduction action test. A single plus-maze trial Experiment 3

Brain Research 887 2000 7–15 www.elsevier.com locate bres Research report Medial prefrontal transection enhances social interaction I: Behavioral studies Luis E. Gonzalez , Maria Rujano, Sonia Tucci, Daniel Paredes, Elizabeth Silva, German Alba, Luis Hernandez Laboratory of Behavioral Physiology , Department of Physiology, School of Medicine, Los Andes University, Merida, Venezuela Accepted 29 August 2000 Abstract Behavioral effects of a medial prefrontal cortex MPFC transection were assessed in animal tests of anxiety. Social investigation and plus-maze open arm exploration increased in MPFC damaged animals relative to sham ones. MPFC lesions prevented D -amphetamine 2 mg kg, i.p. induced social investigation decrease and exaggerated general locomotion increase. Diazepam 1 mg kg, i.p. and MPFC synergistically increased open arm exploration on a second repeated plus-maze trial. These results suggest that the MPFC would be implicated in a generalized mechanism of warning enabling emission of appropriate responses to anxiogenic stimuli. Although, this lesion did not modify motor activity itself, the pattern of the motor activation induced by amphetamine was altered. The role of the MPFC areas in the behavioral response associated with fear is discussed.  2000 Elsevier Science B.V. All rights reserved. Theme : Neural basis of behaviour Topic : Motivation and emotion Keywords : Anxiety; Prefrontal cortex; Amphetamines; Benzodiazepines; Animal model

1. Introduction action test. A single plus-maze trial Experiment 3

allowed a comparative study, in which an independent It has been proposed that reciprocal neural circuits group of animals are confronted with a novel situation. linking the MPFC, the extended amygdala and the hypo- Because it has been previously found that systemic thalamus are directly involved in fear processing and the administration of amphetamine decreases social interaction behavioral response to stress in rats [16,20,30]. In support [40] we assessed whether or not MPFC damage suppresses of this hypothesis, Fos protein has been selectively induced amphetamine effect. To compare the behavioral changes in the MPFC, amygdala, lateral septum and hypothalamus induced by amphetamines [25,40] additional behavioral in anxiety related situations but not in many other types of parameters rearing and self-grooming were scored in behavioral activation [8,43]. Moreover, positron emission control and lesioned animals Experiment 2. tomography studies have shown that the MPFC is con- Finally, systemic administration of benzodiazepines sistently activated during anxiety [18,19,36,52]. does not evoke anxiolytic effect in the plus-maze in mice Although marked effects on social behavior have been or rats with a 5 min previous experience in this test noted [6,45], to the best of our knowledge the social [10,31,37]. However, lesions of subcortical structures interaction test of anxiety has not been used to discriminate interconnected to the MPFC such as the amygdala [12] and effects of MPFC lesions on anxiety. This study evaluates hypothalamus [13] restate sensitivity to the anxiolytic the effect of a surgical MPFC lesion in the social inter- effect of benzodiazepines in this test. On the basis of these observations it was tested whether or not MPFC transec- tion might abolish the typical loss of benzodiazepine effect Corresponding author. Tel.: 158-74-403-110; fax: 158-74-638-304. E-mail address : goreying.ula.ve L.E. Gonzalez. on the plus-maze second trial. Thereby, MPFC damaged 0006-8993 00 – see front matter  2000 Elsevier Science B.V. All rights reserved. P I I : S 0 0 0 6 - 8 9 9 3 0 0 0 2 9 3 1 - 0 8 L rats were treated with benzodiazepines or vehicle and 1900 h. Animals were anesthetized by co-administration of tested on a repeated trial of the elevated plus-maze ketamine and penthothal 110 and 10 mg k i.p., respec- Experiment 4. tively and positioned in a stereotaxic frame David-Kopf Instruments. The skull was exposed and the incisor bar adjusted such that bregma and lambda were at the same

2. Materials and methods height. To lesion the MPFC a knife blade was positioned at