Amphetamine inhibits behavior-related neuronal responses in substantia nigra pars reticulata of rats working for sucrose reinforcement Joshua M. Gulley a , Ann E.K. Kosobud a,b , George V. Rebec a, * a Program in Neural Science, Department of Psychology, Indiana University, 1101 E. 10th Street, Bloomington, IN 47405-7007, USA b Neurology Department, Indiana University School of Medicine, Indianapolis, IN 46202, USA Received 5 November 2001; received in revised form 27 December 2001; accepted 10 January 2002 Abstract Changes in activity of basal ganglia neurons, especially those in the striatum, are thought to underlie the characteristic behavioral patterns produced by d-amphetamine (AMPH). To study the role of the substantia nigra pars reticulata (SNr), a major basal ganglia output nucleus, we recorded from SNr neurons before and after a behaviorally activating dose of AMPH (0.5 mg/kg) in rats trained to nosepoke for sucrose reinforcement. Before AMPH, task-related behaviors were associated primarily with increases or both increases and decreases in SNr firing. Although these same behavior-related patterns persisted after AMPH, their relative magnitude was significantly attenuated. Units unresponsive during task events were unaffected by AMPH. Thus, rather than change the overall level of SNr firing, a behaviorally active dose of AMPH exerts context-dependent effects on the activity of SNr neurons. q 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Substantia nigra pars reticulata; Movement-related neurons; Amphetamine; Behaving rats; Single-unit activity; Nosepoke; Operant behavior As the main output system of the basal ganglia in rats, the substantia nigra pars reticulata (SNr) is strategically posi- tioned to process behavior-related information arising from the striatum [1]. In fact, changes in the activity of striatal neurons are thought to be important for the robust beha- vioral activation produced by psychomotor stimulants such as d-amphetamine (AMPH) and cocaine [10]. It is still uncertain, however, how stimulants act in the SNr to shape behavioral activity. In anesthetized or immobilized rats, systemic AMPH appears to have variable effects in the SNr, eliciting both increases and decreases in response to a range of doses [4,12,15]. Although similar results have been reported for ambulant animals [7,8], it is unclear how these effects relate to movement. In the present experiment, we analyzed AMPH-induced changes in SNr units that responded to specific behavioral events in a conditioned reinforcement task. All animal protocols were approved by the Institutional Animal Care and Use Committee at Indiana University. Male, Sprague–Dawley rats were housed under standard laboratory conditions but food was restricted to 85% of their free-feeding weight (325–450 g). Behavioral training and electrophysiological recording procedures have been described in detail elsewhere [3]. Briefly, rats were placed in a Plexiglas operant chamber and trained in two stages to perform a nosepoke response for access to a 10% w/v sucrose solution. Located on one wall of the chamber was a lickometer equipped with a spout, photobeam, and yellow light-emitting diode (LED) that acted as a feedlight. Two nosepoke operanda, each consisting of a recessed hole with green LEDs and a photobeam, were mounted just above and to the left and right of the spout. Speakers that delivered auditory stimuli were located outside the chamber. Initially, rats were trained to approach and lick the spout tip within 15 s after the onset of a tone cue and the illumina- tion of the feedlight. Valve opening, which led to sucrose delivery for 1 or 1.5 s, was triggered by photobeam breaks at the spout. An intertrial interval (ITI; 10–20 s) followed each sucrose delivery period. If the rat failed to lick within the sucrose-availability interval, the trial was terminated and the ITI commenced. After at least two consecutive sessions Neuroscience Letters 322 (2002) 165–168 0304-3940/02/$ - see front matter q 2002 Elsevier Science Ireland Ltd. All rights reserved. PII: S0304-3940(02)00064-2 www.elsevier.com/locate/neulet * Corresponding author. Tel.: 11-812-855-4832; fax: 11-812- 855-4520. E-mail address: rebec@indiana.edu (G.V. Rebec).