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Effects of a heroin vaccine on heroin self‐administration and its pharmacokinetic correlates (658.5)
Author(s) -
Raleigh Michael,
Pentel Paul,
LeSage Mark
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.658.5
Subject(s) - heroin , self administration , pharmacology , pharmacokinetics , medicine , metabolite , drug
Vaccination with a heroin vaccine (M‐KLH) produced a compensatory increase in heroin self‐administration (HSA) at high heroin unit doses, but a decrease in HSA at low unit doses. Vaccination also blocked heroin‐primed reinstatement of HSA responding during extinction. To study the PK correlate of vaccine‐induced increases in HSA at high unit doses, repeated i.v. heroin injections were administered to vaccinated and control rats that simulated heroin exposure during HSA (0.5 mg/kg/hr heroin in control rats and 1.0 mg/kg/hr heroin in vaccinated rats). 6‐monoacetylmorphine (6‐MAM) and morphine, but not heroin, distribution to brain were reduced in vaccinated rats compared to controls. 6‐MAM concentrations in brain were similar between control rats given 0.5 mg/kg and vaccinated rats given 1.0 mg/kg, suggesting that 6‐MAM was the main heroin metabolite mediating compensation of HSA. These data show that vaccination with M‐KLH altered HSA and reinstatement, that 6‐MAM concentrations in brain mediate these effects, and that high antibody to drug ratios are most effective at reducing heroin’s reinforcing effects. Grant Funding Source : Supported by DA026300, DA030715, and DA07097