Modifications of serotonergic and adrenergic receptor concentrations in the brain of aggressive Canis familiaris Paola Badino a , Rosangela Odore a , Maria C. Osella a , Luciana Bergamasco b , Paola Francone c , Carlo Girardi a , Giovanni Re a, * a Department of Animal Pathology, Division of Pharmacology and Toxicology, University of Torino, Via Leonardo da Vinci, 44, I-10095, Grugliasco (To), Italy b Department of Veterinary Morphology and Physiology, Division of Physiology, University of Torino, Grugliasco (To), Italy c Veterinarian, Public Health Services, A.S.L., Torino, Italy Received 20 February 2004; received in revised form 28 September 2004; accepted 29 September 2004 Abstract The aim of the study was to measure h-adrenergic (h-AR) and serotonergic (5-HTR) receptor concentrations in different brain areas (frontal cortex, hippocampus, hypothalamus and thalamus) of normal and aggressive dogs. Eight adult male dogs, 4.2F0.6 years old, showing no clinical signs but aggression, were used for the study. Eight healthy male dogs, 4.4F0.8 years old, with no history of neurological and/or behavioural disorders and accidental death, were used as controls. The whole frontal cortex, hippocampus, thalamus and hypothalamus were collected after euthanasia and plasma membrane fractions obtained by ultracentrifugation. h-AR and 5-HTR were measured by binding assays using specific radioligand [(À)[ 3 H]CGP 12177 and 5-hydroxy[ 3 H]-tryptamine trifluoroacetate, respectively]. A significant decrease in h-AR levels was observed in the frontal cortex ( P=0.001), hippocampus ( Pb0.0001), and thalamus ( Pb0.0001) of aggressive dogs compared to controls. As far as 5-HTR are concerned, two receptor subtypes were detected. The two subtypes were classified as low-affinity (5-HTR LA) and high-affinity (5-HTR HA) serotonergic receptors for [ 3 H]-hydroxytryptamine, on the basis of their affinity for [ 3 H]-hydroxytryptamine. 5-HTR LA significantly increased in the whole central nervous system (CNS) area of aggressive dogs (frontal cortex P=0.071; hippocampus P=0.0013; thalamus Pb0.0001; hypothalamus P=0.0004); 5-HTR HA significantly increased only in the thalamus ( P=0.0005) and hypothalamus ( P=0.0002). Results suggest the possible role played by the catecholaminergic and serotonergic systems in canine aggressive behaviour. The understanding of the biological basis of canine aggression may enable the development of pharmacological treatments that would target specific neurotransmitter systems. D 2004 Elsevier Inc. All rights reserved. Keywords: Canis familiaris ; Aggression; Brain; Adrenergic receptors; Catecholamine; Serotonergic receptors; Serotonin; Binding assays 1. Introduction Aggression directed toward people is one of the most common reasons why dogs are brought along to veteri- nary behavioural practitioners. Aggression may be the primary manifestation of a distressed animal, since it is the expression of an intricate interaction between innate and learning mechanisms, or the product of a systemic disease (Miczek and Olivier, 1998). In the late 1960s, Moyer (1968) classified aggression into seven main categories, including dominance, fear-induced and territo- rial aggression. Later, Reis (1971) proposed classifying aggression in two main types affective and predatory, whereby all forms of the disorder were included. Since then, other classifications have been proposed (Overall, 1997; Dodman, 1998; Pageat, 1998). As reported by Dodman (1998), affective aggression may be subdivided into offen- sive and defensive subtypes and dominance-related aggres- sions can be considered as the offensive form of affective aggression. Despite the classification criteria, canine aggression should be considered as a serious medical and social 1095-6433/$ - see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.cbpb.2004.09.019 * Corresponding author. Tel.: +39 11 6709014; fax: +39 11 6709017. E-mail address: giovanni.re@unito.it (G. Re). Comparative Biochemistry and Physiology, Part A 139 (2004) 343– 350 www.elsevier.com/locate/cbpa