title: Methylphenidate treatment beyond adolescence maintains increased cocaine self-administration in the spontaneously hypertensive rat model of attention deficit/hyperactivity disorder.
abstract: Past research with the spontaneously hypertensive rat (SHR) model of attention deficit/hyperactivity disorder showed that adolescent methylphenidate treatment enhanced cocaine abuse risk in SHR during adulthood. The acquisition of cocaine self-administration was faster, and cocaine dose-response functions were shifted upward under fixed-ratio and progressive ratio schedules compared to adult SHR that received adolescent vehicle treatment or to control strains that received adolescent methylphenidate treatment. The current study determined if extending treatment beyond adolescence would ameliorate long-term consequences of adolescent methylphenidate treatment on cocaine abuse risk in adult SHR. Treatments (vehicle or 1.5mg/kg/day oral methylphenidate) began on postnatal day 28. Groups of male SHR were treated with vehicle during adolescence and adulthood, with methylphenidate during adolescence and vehicle during adulthood, or with methylphenidate during adolescence and adulthood. The group receiving adolescent-only methylphenidate was switched to vehicle on P56. Cocaine self-administration began on postnatal day 77, and groups receiving methylphenidate during adolescence and adulthood were treated either 1-h before or 1-h after daily sessions. At baseline under a fixed-ratio 1 schedule, cocaine self-administration (2h sessions; 0.3mg/kg unit dose) did not differ among the four treatment groups. Under a progressive ratio schedule (4.5h maximum session length; 0.01-1.0mg/kg unit doses), breakpoints for self-administered cocaine in SHR receiving the adult methylphenidate treatment 1-h pre-session were not different from the vehicle control group. However, compared to the vehicle control group, breakpoints for self-administered cocaine at the 0.3 and 1.0mg/kg unit doses were greater in adult SHR that received adolescent-only methylphenidate or received methylphenidate that was continued into adulthood and administered 1-h post-session. These findings suggest that extending methylphenidate treatment beyond adolescence does not ameliorate explicitly the long-term consequences of adolescent methylphenidate treatment. Pre-session methylphenidate may mask temporarily the detection of an increase in cocaine self-administration following chronic methylphenidate treatment.
authors: Department of Psychological and Brain Sciences, Boston University, Boston, MA 02215, USA.. Electronic address: britahny.baskin@gmail.com.
authors: Britahny M
authors: BM
authors: Baskin
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536 USA. Electronic address: ldwoskin@email.uky.edu.
authors: Linda P
authors: LP
authors: Dwoskin
authors: Department of Psychological and Brain Sciences, Boston University, Boston, MA 02215, USA.. Electronic address: kkantak@bu.edu.
authors: Kathleen M
authors: KM
authors: Kantak
mesh_terms: D000367:Age Factors; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019970:Cocaine-Related Disorders / Q000209:etiology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate
keywords: Adolescence; Attention deficit/hyperactivity disorder; Cocaine; Methylphenidate; Self-administration; Spontaneously hypertensive rat
references: Arch Gen Psychiatry. 1995 Jun;52(6):456-63
references: 7771915
references: Neuropharmacology. 2004;47 Suppl 1:80-91
references: 15464127
references: Nat Neurosci. 2010 Oct;13(10):1161-9
references: 20877280
references: Eur Psychiatry. 2012 Jul;27(5):343-9
references: 22521805
references: Neuropsychopharmacology. 2012 Nov;37(12):2555-65
references: 22805600
references: J Am Acad Child Adolesc Psychiatry. 2013 Mar;52(3):250-63
references: 23452682
references: Clin Psychol Rev. 2011 Apr;31(3):328-41
references: 21382538
references: J Pharmacol Exp Ther. 2009 May;329(2):677-86
references: 19228996
references: Neuropsychopharmacology. 2013 Dec;38(13):2588-97
references: 23822950
references: ACS Chem Neurosci. 2013 Apr 17;4(4):566-74
references: 23402315
references: Addict Biol. 2014 Mar;19(2):145-55
references: 22458761
references: Behav Neurosci. 2008 Apr;122(2):340-57
references: 18410173
references: Neurotoxicol Teratol. 2010 Jul-Aug;32(4):432-42
references: 20347964
references: Biol Psychiatry. 2006 Nov 15;60(10):1111-20
references: 16806100
references: Science. 1983 Aug 19;221(4612):773-5
references: 6879176
references: Behav Pharmacol. 2011 Feb;22(1):31-9
references: 21160423
references: Drug Alcohol Depend. 2007 Feb 23;87(1):20-9
references: 16930863
references: Biochem Pharmacol. 2013 Jul 15;86(2):309-16
references: 23623751
references: Neuropharmacology. 1999 Nov;38(11):1797-804
references: 10587095
references: Am J Psychiatry. 2008 May;165(5):604-9
references: 18381904
references: Neuropsychopharmacology. 2001 Nov;25(5):651-61
references: 11682248
references: Nat Neurosci. 2002 Jan;5(1):13-4
references: 11731802
references: J Neurosci. 2002 Aug 15;22(16):7264-71
references: 12177221
references: Neuropsychopharmacology. 2006 Sep;31(9):1946-56
references: 16319916
references: J Child Adolesc Psychopharmacol. 2004 Summer;14(2):195-206
references: 15319017
references: J Pharmacobiodyn. 1990 Oct;13(10):647-52
references: 2095405
references: Clin Pharmacol Ther. 1999 Sep;66(3):295-305
references: 10511066
references: Behav Brain Res. 2014 Jul 15;268:229-38
references: 24755309
references: Behav Brain Res. 2013 May 1;244:38-47
references: 23376704
references: BMC Psychiatry. 2012;12:219
references: 23216881
references: Biochem Biophys Res Commun. 2010 Jan 15;391(3):1517-21
references: 20035724
references: J Pharmacol Exp Ther. 2000 Oct;295(1):51-7
references: 10991960
references: BMC Psychiatry. 2013;13:237
references: 24074240
references: J Am Acad Child Adolesc Psychiatry. 2010 Dec;49(12):1189-201; quiz 1285
references: 21093769
references: Hippocampus. 2010 Jun;20(6):787-97
references: 19623608
references: Pharmacol Biochem Behav. 1986 Jul;25(1):191-9
references: 3018792
references: Drug Alcohol Depend. 2006 Apr 28;82(2):158-67
references: 16213109
references: Pediatrics. 1982 Jun;69(6):688-94
references: 7079034
references: Trends Pharmacol Sci. 2005 May;26(5):237-43
references: 15860370
references: Behav Pharmacol. 2011 Dec;22(8):794-804
references: 22015805
references: Curr Protoc Neurosci. 2011 Jan;Chapter 9:Unit9.35
references: 21207367
references: Pharmacol Biochem Behav. 2007 Oct;87(4):426-33
references: 17599397
references: Psychopharmacology (Berl). 1990;101(2):262-6
references: 2349367
references: J Pharmacol Exp Ther. 2013 Jun;345(3):374-82
references: 23579044
references: Pharmacol Biochem Behav. 1996 Jan;53(1):5-9
references: 8848459
references: PLoS One. 2012;7(8):e44234
references: 22937166
references: JAMA Psychiatry. 2013 Jul;70(7):740-9
references: 23754458
references: Neurosci Biobehav Rev. 2000 Jun;24(4):417-63
references: 10817843
references: Neuroscience. 2010 Jun 2;167(4):1183-91
references: 20211696
references: Behav Brain Funct. 2005 Dec 15;1:24
references: 16356184
references: Neurosci Biobehav Rev. 2003 Nov;27(7):615-21
references: 14624806
references: Neuropsychopharmacology. 2011 Mar;36(4):837-47
references: 21150910
references: Behav Neural Biol. 1992 Sep;58(2):103-12
references: 1360797
references: Addict Behav. 2014 Jan;39(1):325-8
references: 24090624
references: Neuropharmacology. 2009 Dec;57(7-8):653-64
references: 19733553
references: Biol Psychiatry. 2005 Jun 1;57(11):1239-47
references: 15949994
references: Pediatrics. 2003 Jan;111(1):179-85
references: 12509574
references: Biol Psychiatry. 2003 Dec 15;54(12):1330-7
references: 14675796
references: Eur Arch Psychiatry Clin Neurosci. 2005 Dec;255(6):428-31
references: 16091862
references: Drug Alcohol Depend. 2014 Jul 1;140:25-32
references: 24811203