Premium
Amphetamine‐Induced Dopamine Release in the Rat Striatum: An In Vivo Microdialysis Study
Author(s) -
Butcher Steven P.,
Fairbrother Iain S.,
Kelly John S.,
Arbuthnott Gordon W.
Publication year - 1988
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1988.tb02919.x
Subject(s) - homovanillic acid , microdialysis , amphetamine , nomifensine , dopamine , 3,4 dihydroxyphenylacetic acid , chemistry , pargyline , catecholamine , reserpine , striatum , pharmacology , endocrinology , dopaminergic , medicine , in vivo , neurotransmitter , serotonin , biochemistry , biology , receptor , microbiology and biotechnology
The effects of a number of biochemical and pharmacological manipulations on amphetamine (AMPH)‐induced alterations in dopamine (DA) release and metabolism were examined in the rat striatum using the in vivo brain microdialysis method. Basal striatal dialysate concentrations were: DA, 7 n M; dihydroxyphenylacetic acid (DOPAC), 850 n M; homovanillic acid (HVA), 500 n M; 5‐hydroxyindoleacetic acid (5‐HIAA), 300 n M; and 3‐methoxytyramine (3‐MT), 3 n M . Intraperitoneal injection of AMPH (4 mg/kg) induced a substantial increase in DA efflux, which attained its maximum response 20–40 min after drug injection. On the other hand, DOPAC and HVA efflux declined following AMPH. The DA response, but not those of DOPAC and HVA, was dose dependent within the range of AMPH tested (2–16 mg/kg). High doses of AMPH (>8 mg/kg) also decreased 5‐HIAA and increased 3‐MT efflux. Depletion of vesicular stores of DA using reserpine did not affect significantly AMPH‐induced dopamine efflux. In contrast, prior inhibition of catecholamine synthesis, using α‐methyl‐ p ‐tyrosine, proved to be an effective inhibitor of AMPH‐evoked DA release (<35% of control). Moreover, the DA releasing action of AMPH was facilitated in pargyline‐pretreated animals (220% of control). These data suggest that AMPH releases preferentially a newly synthesised pool of DA. Nomifensine, a DA uptake inhibitor, was an effective inhibitor of AMPH‐induced DA efflux (18% of control). On the other hand, this action of AMPH was facilitated by veratrine and ouabain (200–210% of control). These results suggest that the membrane DA carrier may be involved in the actions of AMPH on DA efflux.