Rats were given 14 “daily” (6 doses/week) s.c. doses of 0.9% NaCl (Sal), morphine (Mor), or methadone (Met), then left untreated for 14 days, and fi nally challenged with Mor, except that half each of the Sal groups were given Sal instead. All the rats were then tested for open fi eld behavior, and were sacrifi ced 2 h post-challenge. Striatal (CPu), accumbal (Acb), sensorimotor cortex (S1) and prefrontal cortex contents of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxytyramine (3 MT, assessed only in the CPu and Acb) were measured by HPLC. Analysis of total distance covered by the rats showed Mor and Met-induced sensitization to Mor in the WHP rats only, whereas the distance covered in the central part of the test arena was signifi cantly affected (increased) only by the Mor pretreatment and only in the WHP rats. There was no signifi cant between-line or treatment-related difference in DA content, and no signifi cant between-line difference in baseline DA metabolite contents, except that S1 HVA content was signifi cantly higher in drug-naive WLP rats than in drug-naive WHP rats. HVA and – to a lesser extent – DOPAC contents were, in general, higher in the Mor-challenged rats than in the respective Sal-treated controls, but the differences were more pronounced in the WLP rats than in their WHP counterparts, whereas the opioid -pretreated WHP rats showed higher CPu and Acb 3 MT contents than their WLP counterparts.
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