Abstract
Rats performed on two multiple random-interval schedules, in which sequences of ascending or descending reinforcement densities were balanced between the schedules and between the two halves of the session. Using a standard reinforcer (10% sucrose pellets), pimozide decreased response rates, while amphetamine increased responding. The effects of both drugs were schedule dependent: larger changes were evident in low response rate, reinforcement-lean components than in high response rate, reinforcement-rich components. Both effects were also time dependent, increasing over the course of the session; this casts serious doubt on the applicability of Herrnstein's matching law for studying agents acting on brain dopamine.
Increasing the period of food deprivation increased response rates, while withdrawing food deprivation decreased responding. These effects were also schedule dependent, but were time independent. Substituting 95% sucrose pellets for standard 10% sucrose pellets caused an immediate and sustained decrease in responding, and up to 10% of earned reinforcement was not consumed. Pimozide increased response rates within reinforcement-lean components and reinstated the complete consumption of earned reward typical of standard reinforcement. These apparently paradoxical effects may be consistent with a decrease in the rewarding properties of sucrose pellets. Despite low response rates, amphetamine did not affect responding maintained by 95% sucrose pellets but did further reduce the consumption of earned reward. These results call into question the generality of the rate-dependency principle in the action of psychomotor stimulants.
Similar content being viewed by others
References
Ahlenius S (1979) An analysis of behavioural effects produced by drug-induced changes of dopaminergic neurotransmission. Scand J Psychol 20:59–64
Beninger RJ (1983) The role of dopamine in locomotor activity and learning. Brain Res Rev 6:173–196
Berlyne DE, Koenig JDV, Hirota T (1966) Novelty, arousal and reinforcement of diversive exploration in the rat. J Comp Physiol Psychol 87:222–226
Blundell JE, Latham CJ (1980) Characterization of adjustments to the structure of feeding behaviour following pharmacological treatment: effects of amphetamine and fenfluramine and the antagonism produced by pimozide and methergoline. Pharmacol Biochem Behav 12:717–720
Bradshaw CM, Szabadi E, Bevan P (1978) Relationships between response rate and reinforcement frequency in variable-interval schedules: the effect of the concentration of sucrose reinforcement. J Exp Anal Behav 19:447–452
Bradshaw CM, Szabadi E, Ruddle HV, Pears E (1983) Herrnstein's equation: effect of deprivation level on performance in variable-interval schedules. Behav Anal Lett 3:267–273
Branch MN (1983) Rate dependency, behavioral mechanisms, and behavioral pharmacology. J Exp Anal Behav 42:511–522
de Villiers PA, Herrnstein RJ (1976) Towards a law of response strength. Psychol Bull 83:1131–1153
Dews PB (1958) Analysis of the effects of pharmacological agents in behavioral terms. Fed Proc 17:1024–1030
Dews PB, Wenger GR (1977) Rate-dependency of the behavioral effects of amphetamine. In: Thompson T, Dews PB (eds) Advances in behavioral pharmacology, Vol 1. Academic Press, New York, pp 167–227
Ettenberg A (1989) Dopamine, neuroleptics and rewarded behavior. Neurosci Biobehav Rev 13:105–111
Ettenberg A, Cinsavich SA, White N (1979) Performance effects with repeated-response measures during pimozide-produced dopamine receptor blockade. Pharmacol Biochem Behav 11:557–561
Ettenberg A, Koob GG, Bloom FE (1981) Response artifact in the measurement of neuroleptic-induced anhedonia. Science 209:357–359
Fibiger HC, Carter DA, Phillips AG (1976) Decreased intracranial self-stimulation after neuroleptics or 6-hydroxydopamine: evidence for mediation by motor deficits rather than reduced reward. Psychopharmacology 47:21–27
Fouriezos G, Wise RA (1976) Pimozide-induced extinction of intracranial self-stimulation: response-patterns rule out motor performance deficits. Brain Res 103:377–380
Fouriezos G, Hansson P, Wise RA (1978) Neuroleptic-induced attenuation of brain-stimulation reward. J Comp Physiol Psychol 92:659–669
Fowler SC (1990) Neuroleptics produce within-session decrements, facts and theories. Drug Dev Res 20:101–116
Franklin KBJ, McCoy SN (1979) Pimozide-induced extinction in rats: Stimulus control of responding rules out a motor deficit. Pharmacol Biochem Behav 11:71–75
Gray T, Wise RA (1980) Effects of pimozide on lever-pressing behavior maintained on an intermittent reinforcement schedule. Pharmacol Biochem Behav 12:931–935
Guttman N (1953) Operant conditioning, extinction, and periodic reinforcement in relation to concentration of sucrose used as reinforcing agent. J Exp Psychol 46:213–224
Hamilton AL, Stellar JR, Hart EB (1985) Reward, performance, and the response strength method in self-stimulating rats: validation and neuroleptics. Physiol Behav 35:897–904
Hawkins TD, Pliskoff SS (1964) Brain-stimulation intensity, rate of self-stimulation, and reinforcement strength: an analysis through chaining. J Exp Anal Behav 7:285–288
Herrnstein RJ (1970) On the law of effect. J Exp Anal Behav 13:243–266
Heyman GM (1983) A parametric evaluation of the hedonic and motoric effects of drugs: pimozide and amphetamine. J Exp Anal Behav 40:113–122
Heyman GM, Seiden LS (1985) A parametric description of amphetamine's effects on response rate: changes in reinforcement efficacy and response topography. Psychopharmacology 85:346–353
Heyman GM, Monaghan M (1987) Effects of changes in response requirement and deprivation on the parameters of the matching law equation: new data and review. J Exp Psychol 13:384–394
Heyman GM, Kinzie DL, Seiden LS (1986) Chlorpromazine and pimozide alter reinforcement efficacy and motor performance. Psychopharmacology 88:346–353
Hill RT (1970) Facilitation of conditioned reinforcement as a mechanism of psychomotor stimulation. In: Costa E, Garrattini S (eds) Amphetamine and related compounds. Raven Press, New York, pp 781–895
Hillegaart V, Ahlenius S, Magnusson O, Fowler CJ (1987) Repeated testing of rats markedly enhances the duration of effects induced by haloperidol on treadmill locomotion, catalepsy, and a conditioned avoidance response. Pharmacol Biochem Behav 27:159–164
Hodos W, Valenstein ES (1962) An evaluation of response rate as a measure of rewarding intracranial stimulation. J Comp Physiol Psychol 53:502–508
Iversen SD (1977) Brain dopamine systems and behaviour. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of Psychopharmacology, Vol. 8. Plenum Press, New York, pp 333–384
Janssen PAJ, Niegemeers CJE, Schellekens KHL (1965) Is it possible to predict the clinical effects of neuroleptic drugs (major transquilisers) from animal data? Arzneimittelforschung 15:104–117
Kelleher RT, Morse WH (1964) Escape behavior and punished behavior. Fed Proc 23:808–817
Kelleher RT, Morse WH (1968) Determinants of the specificity of behavioral effects of drugs. Ergeb Physiol Biol Chem Exp Pharmakol 60:1–56
Lyon MK, Robbins TW (1975) The action of central nervous system drugs: a general theory concerning amphetamine effects. In: Essman W, Valzelli L (eds) Current developments in psychopharmacology. Spectrum, New York, pp 81–163
McDowell JJ, Wood HM (1984) Confirmation of linear system theory prediction: changes in Herrnstein's K as a function of changes in reinforcer magnitude. J Exp Anal Behav 41:183–192
McKearney JW (1974) Effects ofd-amphetamine, morphine and chlorpromazine on responding under fixed-interval schedules of food presentation or electric shock presentation. J Pharmacol Exp Ther 190:141–153
McSweeney FK (1975) Concurrent schedule responding as a function of body weight. Anim Learn Behav 3:264–270
McSweeney FK (1978) Prediction of concurrent key-peck and treadle press responding from simple schedule performance. Anim Learn Behav 6:444–450
Morley MJ, Bradshaw CM, Szabadi E (1984) The effects of pimozide on variable-interval performance: a test of the anhedonia hypothesis of the mode of action of neuroleptics. Psychopharmacology 84:531–536
Morley MJ, Bradshaw CM, Szabadi E (1985) The effect ofd-amphetamine on operant behaviour maintained under variable-interval schedules of reinforcement. Psychopharmacology 87:207–211
Phillips G, Willner P, Muscat R (1991a) Suppression or facilitation of operant behaviour by raclopride depending on concentration of sucrose reward. Psychopharmacology, in press
Phillips G, Willner P, Muscat R (1991b) Reward-dependent suppression or facilitation of consummatory behaviour by raclopride. Psychopharmacology, in press
Robbins TW (1975) The potentiation of conditioned reinforcement by psychomotor stimulant drugs: a test of Hill's hypothesis. Psychopharmacology 45:103–114
Rolls ET, Rolls BJ, Kelly PH, Shaw G, Wood PJ, Dale RI (1974) The relative attenuation of self-stimulation, eating and drinking produced by dopamine-receptor blockade. Psychopharmacology 38:219–230
Salamone JD (1987) The actions of neuroleptic drugs on appetitive instrumental behavior. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of Psychopharmacology, vol 19. Plenum Press, New York, pp 575–608
Sanger DJ (1986) Response decrement patterns after neuroleptic and non-neuroleptic drugs. Psychopharmacology 89:98–104
Seeman P (1980) Brain dopamine receptors. Pharmacol Rev 32:229–243
Snyderman M (1983) Bodyweight and response strength. Behav Anal Lett 3:255–265
Tombaugh TN, Anisman H, Tombaugh J (1980) Extinction and dopamine receptor blockade after intermittent reinforcement training: failure to find functional equivalence. Psychopharmacology 70:19–28
Wetherington CL, Lucas TR (1980) A note on fitting Herrnstein's equation. J Exp Anal Behav 34:199–206
Willner P, Towell A (1982) Microstructural analysis of the involvement of beta-receptors in amphetamine anorexia. Pharmacol Biochem Behav 17:255–262
Willner P, Towell T, Muscat R (1987) Effects of amphetamine and pimozide on reinforcement and motor parameters in variable-interval performance. J Psychopharmacol 1:140–153
Willner P, Phillips G, Muscat R (1989) Time-dependent and schedule-dependent effects of DA receptor blockade. Behav Pharmacol 1:169–176
Willner P, Sampson D, Phillips G, Muscat R (1990) A matching law analysis of the effects of dopamine receptor antagonists on reinforcement and motor parameters in variable-interval performance. Psychopharmacology 101:560–567
Wise RA (1978) Catecholamine theories of reward: a critical review. Brain Res 152:215–247
Wise RA, Spindler J, De Wit H, Gerber GJ (1978) Neuroleptic-induced “anhedonia” in rats: pimozide blocks the reward quality of food. Science 201:262–264
Young PT (1949) Studies of food preference, appetite, and dietary habit. IX. Palatability versus appetite as determinants of the critical concentrations of sucrose and sodium chloride. Comp Psychol Monogr 19:1–44
Young PT, Greene JT (1953) Quantity of food ingested as a measure of relative acceptability. J Comp Physiol Psychol 46:288–294
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Phillips, G., Willner, P., Sampson, D. et al. Time-, schedule-, and reinforcer-dependent effects of pimozide and amphetamine. Psychopharmacology 104, 125–131 (1991). https://doi.org/10.1007/BF02244566
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02244566