PubMed Health⌕ Search

PubMed · 3065827

Evidence for post-synaptic changes mediating increased behavioural sensitivity to dopamine receptor agonists in hypothyroid rats.

Abstract

1. Hypothyroidism was maintained for four weeks in male rats by administration of PTU daily. 2. Hypothyroid rats showed increased behavioural responses to apomorphine, a mixed D1/D2 dopamine receptor agonist, LY 171555, a selective D2 agonist and to SKF 38393, a selective D1 agonist, compared with euthyroid controls. 3. Responses to the selective D1 antagonist, SCH 23390, were decreased, but were increased to the D2 antagonist, haloperidol, in hypothyroid rats. 4. Ligand binding studies showed no significant differences in the affinity and concentration of D1 or D2 receptor sub-types in the striatum of hypothyroid compared with euthyroid rats. 5. However, hypothyroid rats had a greater increase in dopamine stimulated cyclic AMP in the striatum than euthyroid controls. 6. It is concluded that the changes in behavioural sensitivity observed in hypothyroid rats may be associated with these alterations in post-synaptic events.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

A D Crocker, D L Cameron. 1988. Evidence for post-synaptic changes mediating increased behavioural sensitivity to dopamine receptor agonists in hypothyroid rats.. https://doi.org/10.1016/0278-5846(88)90006-1

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Post-pubertal disruption of medial prefrontal cortical dopamine-glutamate interactions in a developmental animal model of schizophrenia.

BACKGROUND: A neonatal ventral hippocampal lesion (NVHL) induces behavioral and physiological anomalies mimicking pathophysiological changes of schizophrenia. Because prefrontal cortical (PFC) pyramidal neurons recorded from adult NVHL rats exhibit abnormal responses to activation of the mesocortical dopaminergic (DA) system, we explored whether these changes are due to an altered DA modulation of pyramidal neurons. METHODS: Whole-cell recordings were used to examine the effects of DA and glutamate agonists on cell excitability in brain slices obtained from pre- (postnatal day [PD] 28-35) and post-pubertal (PD > 61) sham and NVHL animals. RESULTS: N-methyl d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazole propionate (AMPA), and the D(1) agonist SKF38393 increased excitability of deep layer pyramidal neurons in a concentration-dependent manner. The opposite effect was observed with the D(2) agonist quinpirole. The effects of NMDA (but not AMPA) and SKF38393 on cell excitability were significantly higher in slices from NVHL animals, whereas quinpirole decrease of cell excitability was reduced. These differences were not observed in slices from pre-pubertal rats, suggesting that PFC DA and glutamatergic systems become altered after puberty in NVHL rats. CONCLUSIONS: A disruption of PFC dopamine-glutamate interactions might emerge after puberty in brains with an early postnatal deficit in hippocampal inputs, and this disruption could contribute to the manifestation of schizophrenia-like symptoms.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Dopaminergic and adrenergic toxicities on SK-N-MC human neuroblastoma cells are mediated through G protein signaling and oxidative stress.

Dopamine and norepinephrine are neurotransmitters which participate in various regulatory functions of the human brain. These functions are lost in neurodegenerative diseases including Parkinson's disease and Alzheimer's disease. In this study, we used SK-N-MC neuroblastoma cells to investigate the cytotoxicities of high concentrations of dopamine and norepinephrine on neuronal cells. Dopamine, norepinephrine, as well as their corresponding synthetic agonists (SKF38393 and isoproterenol, respectively) triggered SK-N-MC cell death when applied at 50-100 muM persistently for 2 days. This catecholamine-induced cell death appears to be neuronal specific, as demonstrated by their inabilities of triggering apoptosis of A549 lung carcinoma cells and Cos-7 kidney fibroblasts. By pretreating SK-N-MC cells with target-specific inhibitors before administration of catecholamine, components of G protein signaling (i.e. G( s )/cAMP/PKA), monoamine oxidases, nitric oxide synthase, c-Jun N-terminal kinase and oxidative stress were found to be involved in this dopamine/norepinephrine-induced cytotoxicity, which subsequently led to caspase-dependent and -independent apoptotic responses as well as DNA degradation. In contrast, agonists of G( i )-coupled dopamine receptors and adrenergic receptors (quinpirole and UK14,304, respectively) were incapable of triggering apoptosis of SK-N-MC cells. Our results suggest that both G protein (G( s ))-mediated signaling cascade and oxidative stress participate in the dopamine/norepinephrine-induced neuronal apoptosis.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Involvement of dopamine D1 and D2 receptors in the rat nucleus accumbens in immunostimulation.

Analysis of the nature of changes in the immune response in operated Wistar rats showed that electrolytic lesioning of the nucleus accumbens, the site of the greatest density of dopamine D1 and D2 receptors, led to suppression of the immune response in animals immunized with sheep erythrocytes. Administration of SKF 38393 (20 mg/kg) and quinpirol (1 mg/kg), selective agonists of dopamine D1 and D2 receptors respectively, to sham-operated rats induced significant increases in immune responses. However, no immunostimulation was seen on administration of the selective dopamine D2 agonist quinpirol to animals with lesions to the nucleus accumbens as compared with controls. At the same time, treatment of animals with nucleus accumbens lesions using the dopamine D1 receptor agonist SKF 38393 had no effect on the immune response as compared with that in sham-operated animals given the D1 receptor agonist. These data provide evidence that dopamine D2 receptors in the nucleus accumbens have a role in the mechanisms of immunostimulation, though D2 receptors in other brain structures may also make some contribution to this process; D1 receptors in the nucleus accumbens make no significant contribution to controlling the immune response.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗