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Differential Response of Neurotensin to Methamphetamine Self‐Administration
Author(s) -
Frankel Paul S.,
Hoonakker Amanda J.,
Hanson Glen R.
Publication year - 2008
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1432.019
Subject(s) - meth , neurotensin , methamphetamine , dopamine , self administration , dopaminergic , medicine , endocrinology , pharmacology , chemistry , receptor , neuropeptide , monomer , organic chemistry , acrylate , polymer
Neurotensin (NT) is a tridecapeptide associated with extrapyramidal and limbic pathways and is thought to inhibit dopamine (DA) functions in nigrostriatal, mesocortical, and mesolimbic systems. Because of these effects, NT has been referred to as an endogenous neuroleptic. We previously reported that low, high, and multiple doses of psychostimulants such as methamphetamine (METH) have profound effects on tissue levels, expression of associated mRNA, and release of NT in DA‐linked brain structures via activation of DA D‐1 and D‐2 receptors. In order to investigate the potential clinical significance of responses by NT systems to these stimulants, we have examined METH in a self‐administration paradigm and evaluated changes in tissue levels of NT in limbic and extrapyramidal regions. After food training, adult Sprague‐Dawley rats were allowed to self‐administer (i.v.) METH (0.03 or 0.06 mg/0.01 mL) by lever‐pressing (FR = 5) during 4‐hr sessions until a cumulative total of ∼3–4 mg was infused. Animals were sacrificed 6 hr after the last infusion of drug, and NT tissue levels were determined by established RIA techniques. For comparisons, the treatment sessions also included yoked animals that received identical quantities and/or patterns of either METH or saline solution. The results demonstrated four distinct patterns of NT response including (1) regions of no NT changes in either self‐administering or yoked METH groups; (2) regions of comparably increased NT levels in both METH‐treated groups; (3) regions where self‐administration of METH potentiated the increased NT levels relative to yoked METH groups; and (4) a region of increased NT levels only in self‐administering, and not yoked, METH‐treated groups.