Abstract:
RATIONALE:Both methylphenidate (MPH), a catecholamine reuptake blocker, and guanfacine, an alpha2A agonist, are used to treat attention-deficit hyperactivity disorder (ADHD). Childhood impulsivity, including delay discounting, is associated with increased substance use during adolescence. These effects can be mitigated by juvenile exposure to MPH, but less is known about the long-term effects of developmental exposure to guanfacine in males and females. OBJECTIVE:This study aims to determine sex differences and dose-dependent effects of juvenile exposure to MPH or guanfacine on delay-discounting and later cocaine self-administration. METHODS:The dose-dependent effects of vehicle, MPH (0.5, 1, and 2 mg/kg p.o.) or guanfacine (0.003, 0.03, and 0.3 mg/kg, i.p.) on discounting were determined in male and female Sprague-Dawley rats beginning at postnatal day (P)20. At P90, the amount, motivation, and sensitivity to cocaine following early drug exposure were determined with self-administration. RESULTS:Guanfacine, but not MPH, significantly reduced weight by 22.9 ± 4.6% in females. MPH dose dependently decreased delay discounting in both juvenile males and females, while guanfacine was only effective in males. Discounting was associated with cocaine self-administration in vehicle males (R2 = -0.4, P < 0.05) and self-administration was reduced by guanfacine treatment (0.3 mg/kg). Guanfacine significantly decreased cocaine sensitivity in both sexes. CONCLUSIONS:These data suggest that MPH is effective in reducing delay discounting in both sexes. Due to both weight loss and ineffectiveness on discounting in females, guanfacine should be used only in males to reduce delay discounting and later cocaine use.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Freund N,Jordan CJ,Lukkes JL,Norman KJ,Andersen SLdoi
10.1007/s00213-018-5096-0subject
Has Abstractpub_date
2019-02-01 00:00:00pages
685-698issue
2eissn
0033-3158issn
1432-2072pii
10.1007/s00213-018-5096-0journal_volume
236pub_type
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更新日期:2004-05-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
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更新日期:2013-11-01 00:00:00
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pub_type: 杂志文章
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更新日期:1983-01-01 00:00:00