Psychopharmacology(1983) 81 : 18- 23 Psychopharmacology 9 Springer-Verlag 1983 Behavioural Effects of Intracerebral Amphetamine in the Marmoset L. E. Annett, R. M. Ridley, S. J. Gamble, and H. F. Baker Division of Psychiatry, Clinical Research Centre, Watford Road, Harrow, Middlesex HA1 3UJ, UK Abstract. Marmosets were implanted bilaterally with guide cannulae so that d-amphetamine could be delivered to sites within the anterior neostriatum. Six animals received a series of bilateral amphetamine (20 gg) and saline injections to six sites 1 mm apart on a line passing through the caudate and accumbens nuclei. A second group of six animals received a range of doses (0, 5, 10, 20, 40 gg) of amphetamine bilaterally to one caudate and one accumbens site only. Drug injected into the accumbens produced a dose-related increase in checking (small head movements) and locomotion and a decrease in social interaction and inactivity. Drug injected into the caudate did not affect these behaviours, except for checking which was increased by the highest dose. Key words: Intracerebral amphetamine - Accumbens - Caudate - Behaviour - Marmoset Amphetamine abuse by humans may lead to a psychotic state closely resembling schizophrenia (Connell 1958; Bell 1973). Although the behavioural effects of amphetamine have been studied extensively in primates (Randrup and Munkvad 1967; Ellinwood 1971), including marmosets (Scraggs and Ridley 1978; Ridley et al. 1980), there have been few studies of the localisation of these effects within specific brain areas. Studies in rodents have suggested that many of the be- havioural effects of amphetamine are mediated by the striatum, and in particular, that the caudate nucleus and nucleus accumbens are involved in different aspects of amphetamine-induced behaviour (see Iversen 1980). In this experiment we have looked at the effects of direct application of amphetamine to a series of sites within the anterior striatum of the small New World primate, the common marmoset ( Callithrix jacchus). Materials and Methods Subjects. Twelve laboratory born, adolescent male mar- mosets (Callithrixjacchus) weighing 250- 320 g each served as subjects. They were housed in two groups of three and one group of six in large Perspex sided cages (70 x 70 x 80 cm) for the week preceding and throughout the experiment. The daily diet of bread and fruit was given either 1 h before or after the behavioural observations had been made. Monkey chow and water were available throughout the day. Offprint requests to: L. E. Annett Experimental Design. Guide cannulae were implanted bi- laterally at an angle so that in each animal drug could be delivered either to the caudate or accumbens depending on the length of the injection cannulae. An overlapping design was used in which six animals received a series of bilateral amphetamine (20 ~tg) and saline injections to six sites 1 mm apart along the cannula axis (see Fig. 1), and six others received a range of doses (0, 5, 10, 20 and 40 gg) of amphetamine bilaterally to one caudate (site 2) and one accumbens (site 5) site only. Thus for 20 gg amphetamine and saline injections into sites 2 and 5, data was obtained from all 12 animals. In this way the number of injections each animal received was minimised while, at the same time, information about the effect of site and dose of drug was gained from a limited number of animals. Surgery. Guide cannulae (gauge 22), which were 0.5 mm shorter than the shortest injection cannulae, were implanted bilaterally on a line in the coronal plane AP + 12.5 mm (Stephan et al. 1980) inclined at an angle of 20 ~ to the saggital plane crossing the midline 4.2 mm above the interaural line (see Fig. 1). Injection cannulae (gauge 28) of varying lengths could then be used to deliver drugs to sites within the anterior striatum (Cannulae from Clark Electromedical Instruments). Prior to surgery the monkeys' heads were measured stereotactically (under ketamine anaesthesia) and guide and injection cannulae shortened appropriately for each implant. Surgery was performed aseptically under ketamine (0.1 ml, 50 mg/ml IM) followed by nembutal anaesthesia (0.15 ml, 60 mg/ml IP). The skull was exposed by a large semi-circular incision around the occiput. Guide cannulae fitted with injection cannulae were inserted, using the stereotaxic ap- paratus, through a hole drilled in the skull until the tips of the injection cannulae reached the appropriate co-ordinates. The external portions of the guide cannulae, now resting on the skull were fixed to the bone using acrylic cement and small brass screws. Two small holes were made in the skin flap to expose the cannulae before suturing the adjacent skin in- cision. This procedure prevented retraction of the skin and subsequent infection for at least 4 months. Keepers, contain- ing a stylet extending not more than 0.5 mm beyond the tips of the guide cannulae, were screwed onto the guide cannulae and removed only for injections. Injections and Drugs. d-Amphetamine sulphate (Sigma, Poole, Dorset, England) was dissolved in 0.85 % saline for injection. Six marmosets were given bilateral injections' of 20 gg amphetamine and saline to the six sites 1 mm apart (see Fig. 1). Drug and saline injections were given at each site (in a