Effects of cathinone and amphetamine on the neurochemistry of dopamine in vivo.
Male; Animals; Rats; Molecular Structure; Structure-Activity Relationship; Reference Values; Kinetics; Dopamine/*metabolism; Brain/drug effects/*metabolism; Psychotropic Drugs/*pharmacology; Alkaloids/*pharmacology; Amphetamine/*pharmacology; Caudate Nucleus/metabolism; Homovanillic Acid/metabolism; Nucleus Accumbens/metabolism; Putamen/metabolism; Inbred Strains; 3; 4-Dihydroxyphenylacetic Acid/metabolism
The effects of (-)cathinone, the primary psychoactive alkaloid of the Khat plant, were compared to those of (+)amphetamine in the anterior caudate-putamen and the nucleus accumbens. In vivo microdialysis was used to measure extracellular levels of dopamine and metabolites in both regions of the brain simultaneously, after intraperitoneal administration of 0.8, 1.6 or 3.2 mg/kg of either drug (doses expressed as the salts). Both drugs increased levels of dopamine but decreased levels of metabolites in a dose-dependent manner. However, the relative magnitude of these effects depended upon the specific drug, the dose and area of the brain examined. At the largest dose used, amphetamine had a relatively greater effect than cathinone on dopamine in both caudate and accumbens. However, among smaller doses, this difference was only observed in the nucleus accumbens after administration of 1.6 mg/kg. The results also demonstrated a differential regional effect of both drugs at 3.2 mg/kg, in that both had a greater effect on dopamine in the caudate, as opposed to the accumbens. These findings demonstrate a functional heterogeneity of the striatum of the rat, that may be relevant to the understanding of both normal brain function and the neural responses to psychoactive drugs.
Pehek E A; Schechter M D; Yamamoto B K
Neuropharmacology
1990
1990-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0028-3908(90)90041-o" target="_blank" rel="noreferrer noopener">10.1016/0028-3908(90)90041-o</a>
In vivo neurochemical and anatomical heterogeneity of the dopamine uptake system in the rat caudate putamen.
Male; Animals; Rats; Dopamine/*metabolism; Indoles/*pharmacology; Nomifensine/*pharmacology; Homovanillic Acid/metabolism; Electrochemistry; Caudate Nucleus/drug effects/*metabolism; Mazindol/*pharmacology; Neurotransmitter Uptake Inhibitors/*pharmacology; Putamen/drug effects/*metabolism; Inbred Strains; 3; 4-Dihydroxyphenylacetic Acid/metabolism
The neurochemical and anatomical heterogeneity of dopamine uptake blockade was studied at a medial and lateral position in each of 3 rostrocaudal areas of the rat caudate-putamen. In vivo voltammetric measures of extracellular dopamine indicated a lateral-to-medial and rostral-to-caudal gradient in the effect of uptake blockade. The percentage increase in dopamine was greatest in the rostrolateral area (300%) and least in the caudomedial area (10%). The existence of these lateromedial and rostrocaudal gradients was confirmed by tissue content measures of DOPAC and dopamine to DOPAC ratios in each area. The rostrocaudal gradient in the effect of uptake blockade was independent of the rostrocaudal gradient in dopamine tissue content. The regional gradients detected in dopamine uptake blockade may indicate a heterogeneous distribution in the number of uptake sites, a regional variation in the affinity of the uptake site for the blocker and/or altered neuronal activity mediated by an action of the blocker on dopaminergic cell bodies.
Glynn G E; Yamamoto B K
Brain research
1989
1989-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0006-8993(89)90799-3" target="_blank" rel="noreferrer noopener">10.1016/0006-8993(89)90799-3</a>
MPTP neurotoxicity is highly concordant between the sexes among BXD recombinant inbred mouse strains.
*QTL; *Recombinant inbred mice; *Sex Characteristics; *Sex differences; 1-Methyl-4-phenyl-1; 2; 3; 4-Dihydroxyphenylacetic Acid/metabolism; 6-tetrahydropyridine/pharmacology; Animal; Animals; Corpus Striatum/drug effects/*metabolism; Disease Models; Dopamine/metabolism; Female; Gene Expression Regulation/drug effects/*genetics; Glial Fibrillary Acidic Protein/*metabolism; Homovanillic Acid/metabolism; Inbred Strains; Male; Mice; MPTP Poisoning/chemically induced/*pathology; Serotonin/metabolism; Species Specificity; Tyrosine 3-Monooxygenase/metabolism
Continuing our previous work in which we showed wide-ranging strain differences in MPTP neurotoxicity in male mice among ten BXD recombinant inbred strains, we replicated our work in females from nine of the same strains. Mice received a single s.c. injection of 12.5mg/kg MPTP or saline. Forty-eight hours later the striatum was dissected for neurochemical analysis. Striatal dopamine (DA) and its metabolites, DOPAC and HVA, striatal serotonin (5-HT) and its metabolite, 5-HIAA, were analyzed using HPLC. Tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP), an astrocytic protein that increases during the astroglial response to neural injury, were measured using ELISA. There were wide genetic variations in the DA, DOPAC, HVA, TH and GFAP responses to MPTP. We also performed principal component analysis (PCA) on the difference values, saline minus MPTP, for DA, DOPAC, HVA and TH and mapped the dominant principal component to a suggestive QTL on chromosome 1 at the same location that we observed previously for males. Moreover, there were significant correlations between the sexes for the effect of MPTP on DA, HVA, and TH. Our findings suggest that the systems genetic approach as utilized here can help researchers understand the role of sex in individual differences. The same approach can pave the way to understand and pinpoint the genetic bases for individual differences in pathology attributable to toxicants. Such systems genetics approach has broad implications for elucidating gene-environment contributions to neurodegenerative diseases.
Alam Gelareh; Miller Diane B; O'Callaghan James P; Lu Lu; Williams Robert W; Jones Byron C
Neurotoxicology
2016
2016-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.neuro.2016.04.008" target="_blank" rel="noreferrer noopener">10.1016/j.neuro.2016.04.008</a>