Korean J Psychopharmacol.  2000 Jun;11(2):178-187.

Augmentation of Regional Cerebral Blood Flow Response by Repeated Administration of Methamphetamine in Rat

• Jang WS
• Kim JG
• Park JD
• Choi HK
• Chung HS
• Ko SY
• Lee WS

Abstract

OBJECTIVES
It was aimed to observe the regional cerebral blood flow (rCBF) response on methamphetamine challenge test in rats which were subjected to repeated administration of methamphetamine, and to investigate the mechanism(s) of changes in rCBF response in relation to the dopaminergic receptors and cyclic AMP.
METHODS
Male Sprague-Dawley rats received daily injections of methamphetamine (0.3 mg/kg, i.p.) for 10 days, and were then allowed a 4-day drug-free period. Naive and methamphetamine-pretreated rats were challenged with topical application of methamphetamine on the surface of parietal cortex through a cranial window. The changes in rCBF were measured by laser-Doppler flowmetry.
RESULTS
Acute topical application of methamphetamine dose-dependently increased rCBF with little effect on mean arterial blood pressure. The methamphetamine-induced increases in rCBF were significantly blocked by SCH23390, a D1-like receptor antagonist, but not by sulpiride, a D2-like receptor antagonist. Repeated administration of methamphetamine induced progressive augmentation of rCBF in response to the challenge of methamphetamine. Repeated administration of methamphetamine in combination with SKF38393, a D1-like receptor agonist, as well as with SCH23390 significantly attenuated the development of augmentation of rCBF response to methamphetamine. The augmentation of rCBF response was markedly inhibited by pretreatment with 2',3'-dideoxyadenosine, a specific adenylyl cyclase inhibitor, and Rp-cAMPS, a protein kinase A inhibitor, respectively.
CONCLUSION
Based on these results, it is suggested that repeated administration of methamphetamine induces an augmentation of rCBF in response to the challenge of methamphetamine, and that D1-like receptor-mediated cyclic AMP plays a critical role in the development of augmentation of methamphetamine-induced rCBF response.

Keyword

Methamphetamine; Cerebral blood flow; D1-like receptor cyclic AMP

MeSH Terms

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
Adenylyl Cyclases
Animals
Arterial Pressure
Cyclic AMP
Cyclic AMP-Dependent Protein Kinases
Dideoxyadenosine
Humans
Laser-Doppler Flowmetry
Male
Methamphetamine*
Rabeprazole
Rats*
Rats, Sprague-Dawley
Sulpiride
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
Cyclic AMP
Cyclic AMP-Dependent Protein Kinases
Dideoxyadenosine
Methamphetamine
Sulpiride