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Author Topic: Long-lasting dopamine receptor UP-REGULATION in amphetamine-treated rats ...  (Read 1051 times)

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... following amphetamine neurotoxicity

source: https://www.ncbi.nlm.nih.gov/pubmed/1816575

Long-lasting dopamine receptorWiki up-regulation in amphetamine-treated rats following amphetamine neurotoxicity

Abstract

Amphetamine (A) (9.2 mg/kg, IP), in combination with iprindoleWiki (I) (10.0 mg/kg, IP), caused long-lasting dopamine (DA) depletions in striatum (-49%, 4 weeks) but not in nucleus accumbens following one A/I injection.

Striatal DA had recovered by 4 months. DA receptors (DAr) were up-regulated: 1) behavioral responses to a DA receptor agonist (apomorphine) were significantly elevated.

These included apomorphine-induced locomotor activity (+103% and +160%, on weeks 3 and 10) and apomorphine-induced stereotypy (day 10). 2) Bmax for [3H]spiroperidol binding to striatal D2 DAr (12 weeks) increased (+53%, week 12). Injection of the DAr neuromodulator cyclo(leucyl-glycyl) (8 mg/kg/day x 4 days, SC) reversed the Bmax increase.

Thus toxicity (DA depletion) following high-dose amphetamine appears to induce compensatory changes in DAr. This DAr upregulation may explain the lack of abnormal movements despite enduring DA depletion.

Additionally, the A/I paradigm as an animal model of long-lasting DAr up-regulation, could be used to screen neuromodulatory agents, like CLG, that might treat disorders (e.g., tardive dyskinesia and schizophrenia) thought to involve up-regulated DAr.
I do not condone or support any illegal activities. All information is for theoretical discussion and wonder.
All activities discussed are considered fictional and hypothetical. Information of all discussion has been derived from online research and in the spirit of personal Freedom.

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