Abstract:
:To analyze the involvement of dopamine (DA) and serotonin (5-HT) release in the stimulus properties of methamphetamine, two amphetamine analogs that selectively release either brain DA (phentermine) or 5-HT (fenfluramine) were tested for their ability to substitute for methamphetamine in rats discriminating methamphetamine (1.0 mg/kg) from saline. They were subsequently tested for their ability to alter IV methamphetamine (0.06 mg/kg per injection) self-administration in the same species when given as a pretreatment. The DA releaser phentermine, like methamphetamine itself, decreased methamphetamine self-administration (to 70% of baseline responding), but only at a dose of 3.0 mg/kg that fully generalized to the methamphetamine stimulus in the discrimination study. The 5-HT releaser fenfluramine attenuated methamphetamine self-administration to a much larger extent than phentermine (to 37% of baseline responding) at a dose of 1.8 mg/kg that did not generalize to methamphetamine and did not decrease rate of responding in the discrimination study. Tolerance developed to the inhibitory effect of 1.8 mg/kg fenfluramine on methamphetamine self-administration when it was given repeatedly over four consecutive daily sessions. The fenfluramine-induced decrease in methamphetamine self-administration was also attenuated when it was given together with the small 1.0 mg/kg dose of phentermine. These results suggest that DA release plays a dominant role in the discriminative stimulus effects of methamphetamine. However, stimulation of 5-HT release can strongly modify methamphetamine self-administration.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Munzar P,Baumann MH,Shoaib M,Goldberg SRdoi
10.1007/s002130050836subject
Has Abstractpub_date
1999-01-01 00:00:00pages
287-96issue
3eissn
0033-3158issn
1432-2072journal_volume
141pub_type
杂志文章abstract:RATIONALE:Recent findings have shown a complexly regulated 5-HT system as it is linked to different kinds of aggression. OBJECTIVE:We focus on (1) phasic and tonic changes of 5-HT and (2) state and trait of aggression, and emphasize the different receptor subtypes, their role in specific brain regions, feed-back regul...
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