title: The psychopharmacology of impulsive behaviour in rats VIII: effects of amphetamine, methylphenidate, and other drugs on responding maintained by a fixed consecutive number avoidance schedule.
abstract: BACKGROUND
  Impulsive behaviour is a component of psychiatric disorders such as bipolar disorder, attention deficit hyperactivity disorder (ADHD), or personality disorders. Most experimental studies on impulsive behaviour punish impulsive choices by loss or delay of reward. In the present study, impulsive behaviour was punished by an explicitly aversive stimulus, using a novel fixed consecutive number (FCN) schedule of electric shock avoidance.
  
  
  OBJECTIVE
  This study was conducted to demonstrate stable performance using the FCN avoidance procedure, and examine the effects of drugs previously shown to affect impulsive behaviour using a conventional FCN schedule.
  
  
  METHODS
  First, rats were trained in the appetitive FCN procedure. Pressing the right lever in an operant conditioning chamber after having pressed the left lever at least six times delivered a food pellet (FCN6). Responses on the right lever before completing this ratio resulted in a time out and restarted the ratio. The rats were then switched to FCN avoidance. Responses on the right lever made before completion of the ratio also resulted in food delivery, but were accompanied by an electric shock.
  
  
  RESULTS
  Chlordiazepoxide (10.0 mg/kg), ethanol (1.0 g/kg), and haloperidol (0.1 mg/kg) increased impulsive behaviour by reducing the number of left lever responses made before the right lever was pressed. Imipramine (1.0-10.0 mg/kg) and desipramine (1.0-10.0 mg/kg) had no effect on impulsive choice. Amphetamine (0.4 and 0.8 mg/kg) and methylphenidate (6.0 mg/kg) significantly increased the mean chain length, and the proportion of very long chains, indicative of reduced impulsivity, although this did not improve efficiency.
  
  
  CONCLUSIONS
  The increases in impulsivity produced by chlordiazepoxide, ethanol, and haloperidol were similar to those under appetitive FCN schedules. In contrast, amphetamine and methylphenidate, by reducing impulsivity in the FCN avoidance, induced effects opposite to those observed in an appetitive FCN procedure. These results suggest that the therapeutic actions of stimulants, to reduce impulsive behaviour in ADHD, may arise in part by increasing the control of behaviour by aversive stimuli.
authors.affiliation: CNS Discovery, AstraZeneca R & D Wilmington, Wilmington, DE 19850, USA. john.evenden@astrazeneca.com
authors.forename: John
authors.initials: J
authors.lastname: Evenden
authors.forename: Tracey
authors.initials: T
authors.lastname: Ko
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002707:Chlordiazepoxide / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D008774:Methylphenidate / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D012055:Reinforcement Schedule
chemical_list: D008774:Methylphenidate; D000431:Ethanol; D002707:Chlordiazepoxide; D006220:Haloperidol; D007099:Imipramine; D003913:Dextroamphetamine
references.citation: Psychopharmacology (Berl). 1997 Jan;129(2):141-52
references.pmid: 9040120
references.citation: Psychopharmacology (Berl). 1998 Dec;140(3):319-30
references.pmid: 9877012
references.citation: J Pharmacol Exp Ther. 1979 May;209(2):309-15
references.pmid: 108387
references.citation: Psychopharmacology (Berl). 1991;105(2):253-8
references.pmid: 1796131
references.citation: Psychopharmacology (Berl). 1999 Oct;146(4):348-61
references.pmid: 10550486
references.citation: Am J Psychiatry. 1996 Sep;153(9):1147-53
references.pmid: 8780417
references.citation: Psychopharmacology (Berl). 1996 Nov;128(2):161-70
references.pmid: 8956377
references.citation: J Pharmacol Exp Ther. 1972 Oct;183(1):1-13
references.pmid: 5080032
references.citation: Behav Brain Res. 2002 Mar 10;130(1-2):65-71
references.pmid: 11864719
references.citation: Psychopharmacology (Berl). 1998 Aug;138(3-4):295-304
references.pmid: 9725751
references.citation: Behav Brain Res. 1998 Jul;94(1):127-52
references.pmid: 9708845
references.citation: Psychopharmacology (Berl). 2000 Nov;152(4):362-75
references.pmid: 11140328
references.citation: Psychopharmacology (Berl). 1998 Aug;138(3-4):283-94
references.pmid: 9725750
references.citation: Psychopharmacology (Berl). 1984;84(3):405-12
references.pmid: 6440188
references.citation: J Psychopharmacol. 2003 Sep;17(3):332-6
references.pmid: 14513926
references.citation: J Exp Anal Behav. 1963 Jul;6:331-42
references.pmid: 13934336
references.citation: Pharmacol Biochem Behav. 1999 May;63(1):71-82
references.pmid: 10340526
references.citation: J Pharmacol Exp Ther. 1983 Jan;224(1):80-8
references.pmid: 6848751