Cross-sensitization of the reinforcing effects of cocaine and amphetamine in rats.
BACKGROUND
Cross-sensitization between cocaine and amphetamine has been demonstrated in different behavioral paradigms. There is a relative paucity of studies examining whether cross-sensitization occurs between amphetamine and cocaine when both are self-administered.


OBJECTIVE
The current study was designed to test whether animals sensitized to the reinforcing effects of cocaine would show cross-sensitization of the reinforcing effects of amphetamine, using a self-administration paradigm.


METHODS
Male, Sprague-Dawley rats were trained to self-administer cocaine and given limited or high exposure to cocaine under a fixed ratio (FR) 1 procedure. After the initial exposure to cocaine, animals self-administered cocaine (1.5 mg/kg per injection) under a progressive ratio (PR) procedure. Subsequently, breakpoints on a PR schedule and rates of intake on an FR schedule maintained by different doses of amphetamine were assessed.


RESULTS
Animals with high initial exposure to cocaine (40 injections of 1.5 mg/kg per injection per day for 5 days) showed stable breakpoints throughout testing. Animals given limited initial cocaine exposure (20 injections of 0.75 mg/kg per injection for 1 day) produced a gradual increase in breakpoints maintained by cocaine over time (i.e., sensitization of the reinforcing effects of cocaine). When subsequently tested with amphetamine, the dose-effect curve was shifted upward in the limited-exposure group relative to the high-exposure group, suggesting cross-sensitization of the reinforcing effects of amphetamine.


CONCLUSIONS
Sensitization of the reinforcing effects of cocaine resulted in cross-sensitization of the reinforcing effects of amphetamine. This phenomenon occurs even when both drugs are self-administered.
Liu
Yu
Y
Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center Blvd., Winston-Salem, NC 27157, USA.
Morgan
Drake
D
Roberts
David C S
DC
D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration
D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D000661:Amphetamine; D003042:Cocaine
Psychopharmacology (Berl). 1995 Feb;117(3):262-6
7770601
Science. 1991 Mar 29;251(5001):1580-6
2011738
Pharmacol Biochem Behav. 1994 Jan;47(1):203-5
8115423
Eur Neuropsychopharmacol. 2007 Apr;17(5):352-7
17029912
Life Sci. 1997;60(1):PL1-7
8995535
Pharmacol Biochem Behav. 1983 Jan;18(1):123-7
6828530
J Neurosci Methods. 1996 May;66(1):1-11
8794935
Psychopharmacology (Berl). 1977 Apr 29;52(2):185-90
407604
J Pharmacol Exp Ther. 1988 Jun;245(3):1095-102
3385638
Psychopharmacology (Berl). 2007 Apr;191(3):653-67
16932924
J Pharmacol Exp Ther. 1995 May;273(2):808-15
7752084
Neuropsychopharmacology. 2004 Dec;29(12):2149-59
15266353
Eur J Neurosci. 2005 Jul;22(1):195-200
16029209
Brain Res. 2007 Jul 9;1157:1-10
17544385
Psychopharmacology (Berl). 1993;112(2-3):343-51
7871040
Psychopharmacology (Berl). 1992;107(2-3):271-6
1615126
Psychopharmacology (Berl). 1991;103(1):62-6
1672461
Biol Psychiatry. 1983 Apr;18(4):429-40
6860719
Neuropsychopharmacology. 2002 Nov;27(5):813-25
12431855
J Neurosci. 2003 Apr 15;23(8):3531-7
12716962
J Neurosci. 1999 Nov 1;19(21):9579-86
10531460
Psychopharmacology (Berl). 1989;98(3):357-62
2546170
Am J Psychiatry. 1975 Mar;132(3):225-31
1115261
J Exp Anal Behav. 1994 Mar;61(2):169-80
7513346
Psychopharmacology (Berl). 1997 Sep;133(1):7-16
9335075
Neuropsychopharmacology. 2006 Jan;31(1):121-8
15920502
Neuropsychopharmacology. 2002 Dec;27(6):970-9
12464454
JAMA. 1967 Jul 31;201(5):305-9
6071725
Neuropsychopharmacology. 2003 Apr;28(4):629-39
12655307
Am J Psychiatry. 1976 Jun;133(6):627-34
776007