Early withdrawal from repeated cocaine administration upregulates muscarinic and dopaminergic D2-like receptors in rat neostriatum.
The present results show an increase in locomotor activity 24 h following repeated cocaine administration only with the higher dose (10 mg/kg, i.p., daily for 1 week) compared to controls (administered with saline). Binding assays were done and the ligands used were [3H]N-methylscopolamine ([3H]-NMS), [3H]-SCH 23390, and [3H]-spiroperidol to determine muscarinic (M1- and M2-like), D1 and D2 receptors, respectively. Scatchard analyses revealed alterations in Bmax not only for muscarinic, but also for D2-like receptors that were significantly increased. On the other hand, no alterations were detected on D1-like receptors densities and dissociation constant values. However, the Kd value was significantly increased for D2 receptors. The changes in muscarinic receptors were observed predominantly on M2-like, which presented an increase of 84% with the 10 mg/kg, i.p., dose only. On D2-like receptors, increases of 63 and 54% were demonstrated with the doses of 5 and 10 mg/kg, i.p.. The preferential effects of cocaine on muscarinic and D2-like receptors were also demonstrated in vitro where decreases in [3H]-NMS and [3H]-spiroperidol binding were observed. The results indicate that the effects of cocaine on muscarinic and dopaminergic postsynaptic receptors are functions of dose, duration of treatment, and time of drug withdrawal.
Sousa
F C
FC
Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil.
Gomes
P B
PB
Macêdo
D S
DS
Marinho
M M
MM
Viana
G S
GS
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D015854:Up-Regulation