Effects of isradipine, a dihydropyridine-class calcium-channel antagonist, on d-methamphetamine's subjective and reinforcing effects.
In healthy human volunteers, we have previously shown that isradipine, a dihydropyridine-class calcium-channel antagonist, reduces some methamphetamine-induced positive subjective effects associated with its abuse liability, presumably by antagonizing cortico-mesolimbic dopamine pathways. In the present study, we combined acute immediate-release (IR) isradipine with repeated sustained-release (SR) isradipine pretreatment to determine whether isradipine could antagonize methamphetamine's positive subjective and reinforcing effects in methamphetamine-dependent research subjects. We included 18 non-treatment-seeking, methamphetamine-dependent subjects aged between 18 and 51 years in this double-blind, within-subject, cross-over study, which was done in a human laboratory. Intravenous methamphetamine (0, 15 and 30 mg) was administered on three different days after 5 days of double-blind cross-over treatment with either isradipine or matching placebo. Subjects received oral isradipine 30 mg SR at bedtime, plus 15 mg IR administered 2 h before methamphetamine infusion. Self-report questionnaires measured drug liking, euphoria, craving, stimulation, and methamphetamine preference. Methamphetamine reinforcement was measured by a behavioural procedure involving choices between methamphetamine and money. For those who received isradipine second and placebo first as the pretreatment paradigm but not vice versa, methamphetamine-induced drug liking, elation, and preference were reduced significantly by isradipine. Depending upon conditioning status, isradipine can reduce some methamphetamine-induced positive subjective and reinforcing effects associated with its abuse liability in methamphetamine addicts.
Johnson
Bankole A
BA
Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. bankolejohnson@virginia.edu
Roache
John D
JD
Ait-Daoud
Nassima
N
Wallace
Christopher
C
Wells
Lynda
L
Dawes
Michael
M
Wang
Yanmei
Y
D000293:Adolescent; D000328:Adult; D019969:Amphetamine-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology; D000704:Analysis of Variance; D019540:Area Under Curve; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D017275:Isradipine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012054:Reinforcement, Psychology; D011795:Surveys and Questionnaires; D013997:Time Factors
D002121:Calcium Channel Blockers; D017275:Isradipine