NUCLEUS ACCUMBENS DOPAMINE DEPLETIONS MAKE ANIMALS HIGHLY SENSITIVE TO HIGH FIXED RATIO REQUIREMENTS BUT DO NOT IMPAIR PRIMARY FOOD REINFORCEMENT J. D. SALAMONE,* A. WISNIECKI, B. B. CARLSON and M. CORREA Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA AbstractöIt has been suggested that dopamine in nucleus accumbens is involved in the process of enabling organisms to overcome work-related response costs. One way of controlling work costs with operant schedules is to use ¢xed ratio schedules with di¡erent ratio requirements. In the present study, the e¡ects of nucleus accumbens dopamine depletions were investigated using six schedules: ¢xed ratio 5, 20, 50, 100, 200, and 300. In the ¢rst three schedules the food reinforcement consisted of one 45 mg food pellet per ratio completed. In the remaining schedules the food reinforcement per ratio completed was increased to two pellets for ¢xed ratio 100, four pellets for ¢xed ratio 200, and six pellets for ¢xed ratio 300. All rats were trained extensively prior to surgery, and rats were able to maintain high levels of responding on all schedules up to the ¢xed ratio 300. After training, rats were injected with either ascorbate vehicle or 6-hydroxydop- amine into the nucleus accumbens. Rats were tested post-surgically on each of the schedules, with 3 days of testing per schedule. Rats with nucleus accumbens dopamine depletions exhibited behavioral de¢cits that were highly dependent upon the ratio value. There were small and transient e¡ects of dopamine depletion on ¢xed ratio 5 lever pressing, but as the ratio value got larger the impairment became greater. On the ¢xed ratio 20 and 50 schedules, response rates were partially reduced in dopamine-depleted rats. Responding on the ¢xed ratio 200 and 300 schedules was severely impaired, and on the last day of ¢xed ratio 300 testing no dopamine-depleted rats obtained a single reinforcer. These data are consistent with previous reports that accumbens dopamine depletions enhance `ratio strain', making rats more sensitive to high ratio values. The induction of ratio strain by dopamine depletions does not appear to be related to a loss of appetite, and seems to be relatively independent of the baseline rate of responding and the overall density of food reinforcement across the session. We conclude that dopamine in nucleus accumbens may be important for enabling rats to overcome behavioral con- straints such as work-related response costs, and may be critical for the behavioral organization and conditioning pro- cesses that enable animals to emit large numbers of responses in the absence of primary reinforcement. ß 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved. Key words: operant, fatigue behavior, motivation, behavioral economics, reward. The behavioral functions of nucleus accumbens dopa- mine (DA) continue to be the subject of great interest in neuroscience. It was suggested for many years that accumbens DA mediates the reinforcing e¡ects of drugs of abuse (e.g. Wise, 1982; Caine and Koob, 1994), as well as the primary reinforcing characteristics of natural reinforcers such as food (Wise et al., 1978; Wise, 1982; Hernandez and Hoebel, 1988; Smith, 1995). Yet despite the longevity and popularity of this view, there is now a considerable body of evidence demonstrating that accumbens DA does not mediate primary food reinforce- ment or motivation (Caine and Koob, 1994; Roberts et al., 1977; for reviews see Salamone, 1987, 1991, 1992; Salamone et al., 1997, 1999). In fact, there is little evi- dence to indicate that performance on some operant tasks can be a¡ected by accumbens DA depletions because of impairment in primary food reinforcement or motivation. For example, although performance on the continuous reinforcement schedule is highly depen- dent upon primary reinforcement and food motivation (Salamone et al., 1991; Aberman and Salamone, 1999), overall response output on this schedule was relatively una¡ected by accumbens DA depletions (McCullough et al., 1993; Salamone et al., 1995; Aberman and Salamone, 1999). The e¡ects of accumbens DA deple- tions that have been seen with some operant schedules were shown not to resemble the e¡ects of extinction (McCullough et al., 1993; Salamone et al., 1995; for review see Salamone et al., 1997), and also did not resemble the e¡ects of prefeeding to reduce food motiva- tion (Salamone et al., 1991; Aberman and Salamone, 1999). Depletions of DA in nucleus accumbens did not suppress food intake (Koob et al., 1978; Salamone et al., 1993a), and failed to a¡ect several parameters of feeding behavior, including total food intake, time spent feeding, feeding rate, or forepaw usage during food handling 863 *Corresponding author. Tel. : +1-860-486-4302 ; fax : +1-860-486- 2760. E-mail address : salamone@psych.psy.uconn.edu (J. D. Salamone). Abbreviations : ANOVA, analysis of variance ; DA, dopamine ; EDTA, ethylenediaminetetra-acetate; FR, ¢xed ratio; n.s., not signi¢cant ; 6-OHDA, 6-hydroxydopamine. NSC 5092 21-8-01 www.elsevier.com/locate/neuroscience Neuroscience Vol. 105, No. 4, pp. 863^870, 2001 ß 2001 IBRO. Published by Elsevier Science Ltd Printed in Great Britain. All rights reserved PII:S0306-4522(01)00249-4 0306-4522 / 01 $20.00+0.00