Pharmacolo~,y Biochemi.stry& Behavior, Vol. 17, pp. 445-450, 1982. Printedin the U.S.A. Behavioral Observation and Intracerebral Electrochemical Recording Following Administration of Amphetamine in Rats J. D. SALAMONE,* W. S. LINDSAY,+ D. B. NEILL *~ AND J. B. JUSTICE+ Departments of *Psychology and +Chemistt3,, Emoo' University, Atlanta, GA 30322 Received 1 July 1981 SALAMONE, J. D., W. S. LINDSAY, D. B. NE1LL AND J. B. JUSTICE. Behavioral observation and intracerebral electrochemi('al re('ordin~, fldlowing admini.~tration of amphetamine in rat.~. PHARMAC. BIOCHEM. BEHAV. 17(3) 445-450. 1982.--lntracerebral electrochemistry (chronoamperometry) was performed on rats that were administered 1, 4, and 8 mg/kg doses of amphetamine. Graphpoxy working electrodes were implanted bilaterally in nucleus accumbens (ACC) and ventral anterior striatum (VAS). Following drug injection, locomotor and stereotyped behaviors were observed. lntracerebral electrochemical signals reliably increased following injection of amphetamine. The magnitude of these in- creases did not change significantly across the dose range tested for VAS electrodes. ACC electrodes had increases similar in magnitude to VAS electrodes at 1 and 4 mg/kg. At 8 mg/kg increases obtained from ACC electrodes were significantly lower than those recorded from VAS. Onset of the change in electrochemical signal paralleled the onset of activity or stereotypy but the subsequent declines in signal and behavior were only loosely correlated. At the 4 mg/kg dose, the magnitude of signal increase from striatum was negatively correlated with indices of stereotypy and positively correlated with locomotor counts. Intracerebral electrochemistry Striatum Locomotion Amphetamine Dopamine Stereotypy Nucleus accumbens AMPHETAMINE is a phenethylamine whose pharmacolog- ical and behavioral effects have been widely studied. The drug is known to stimulate release and block reuptake of central nervous system dopamine (DA) and norepinephrine [4,6]. DA in particular has been implicated as a central mediator of some of the behavioral effects of amphetamine, including increased locomotion and stereotyped behavior [10l. Evidence indicates that different DA terminal areas mediate amphetamine-induced locomotion and stereotypy. Reduction of neostriatal DA with intrastriatal injections of 6-hydroxydopamine (6-OHDA) attenuates amphetamine stereotypy while not affecting amphetamine locomotion [ 11 ]. In contrast, 6-OHDA injections into nucleus accumbens (ACC), another DA terminal region, decrease am- phetamine-produced locomotion, but no stereotypy [11]. Injection of amphetamine or DA directly into ACC stimu- lates locomotor activity [21], while intrastriatal DA applica- tion induces the sniffing and biting response characteristic of stereotypy [5]. Despite extensive data on the behavioral and neurochem- ical results of amphetamine administration, little is known about the pattern of neurotransmitter activity during the course of drug-induced behavior. The majority of studies on amphetamine neuropharmacology have employed tissue punches, tissue slices, or synaptosomal preparations, and thus preclude direct comparison with behavioral events. Push-pull cannula methodology allows for assessment of neurotransmitter release in an intact organism [19] but few such studies have provided detailed comparisons with the be- havior of the organism. For these reasons, intracerebral (also known as in vivo) electrochemistry has been receiving much attention recently. Intracerebral electrochemistry involves the monitoring of compounds via electrodes chronically im- planted in the brain. This technique was originally developed by Adams [1], and is continuing as a focal research area in a number of laboratories [3, 7, 14, 15, 18]. Intracerebral electrochemical recording in DA terminal areas following amphetamine administration has been re- ported previously [3, 7, 9]. Huffet al. [9] recorded increases in neostriatal electrochemical signals following injection of a variety of doses of amphetamine. Unilateral destruction of the nigrostriatal DA systems with 6-OHDA attenuates the amphetamine-induced increase in the striatal signal on the lesioned side [7]. No behavioral observations were reported in these experiments. In the present study, intracerebral electrochemistry was performed via electrodes implanted in ventral anterior striatum (VAS) and ACC while the behavior of the subjects was observed. The doses of amphetamine used were chosen ~Send reprint requests to Darryl B. Neill, Department of Psychology, Emory University, Atlanta, GA 30322. 445