Mechanisms of Dopamine Release From Rat Striatum and Nucleus Accumbens Slices:The Role of Transporters, Receptors and Membrane Depolarization
Abstract
The striatum (STR) and nucleus accumbens (NACC) are major terminal fields of dopaminergic neurons originating in the midbrain. In rat brain, most studies of the characteristics of dopamine (DA) neurons have utilized the striatum (STR) because of its greater size. However, the STR and NACC subserve different functions. In this dissertation, the STR and NACC were compared directly with respect to the release of [3H)DA and endogenous DA from superfused slices in vitro in response to elevated potassium, excitatory amino acids, serotonin (5-HT), and D-amphetamine. To assist in evaluating the contribution of intrinsic neuronal circuitry on overflow of [3H]DA, the effects of alterations in cation concentration, antagonists selective for various relevant receptors , and an inhibitor of interneuronal activity were tested. The validity of measuring overflow of [3H)DA was tested by measuring overflow of endogenous DA under some of the same conditions. Under basal conditions, [3H]DA overflow was greater in STR than in NACC. Blockade of DA re-uptake enhanced overflow by 31 % in NACC and 55% in STR. Removal of Ca reduced overflow by >50% in both regions. In the NACC, tetrodotoxin (TTX) reduced, and Mg-free buffer increased overflow of [3H]DA. Release stimulated by elevated potassium (K) had characteristics consistent with exocytotic release. K-stimulated release was strongly reduced (80%) by removal of Ca and enhanced by removal of Mg in both STR and NACC. Elevated K released more [3H]DA in NACC (9.0%) than in STR (4.8%). TTX enhanced (33%) K-stimulated release in STR but reduced (82%) release in NACC. Activation of glutamate or GABAA receptors was not an important contributor to K-stimulated release. K-stimulated release was not affected by transporter blockade except for inhibition of release observed in the NACC by GBR 12909. Release stimulated by L-glutamate had characteristics consistent with exocytotic release.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 21, 1992
- Accession Number
- AD1011105
Entities
People
- Henry Iii M. Jacocks
Organizations
- Uniformed Services University of the Health Sciences