Effects of cerebral depletion of norepinephrine on conditioned avoidance responding in Sprague-Dawley and Fischer rats

Martin, Gregory E.; Elgin, Robert J.

doi:10.1016/0091-3057(88)90436-4

Cited by 5 publications

(1 citation statement)

References 15 publications

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“…Although to date there is no report about effects of CPT on serotonergic neurons in vitro or in vivo , the result of DSP4 is in agreement with previous studies in that DSP4 did not change the amount of 5-hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid in the hippocampus (Jackisch et al 2008) and dorsal raphe nucleus (Cassano et al 2009). Also, previous studies have demonstrated that DSP4 treatment of Fischer 344 rats affects only noradrenergic neurons, leaving serotonergic and dopaminergic neurons intact (Chrobak et al 1985, Martin & Elgin 1988). However, it was reported that DSP4 could induce a decrease of 5-HT concentrations in the cerebral cortex, mesencephalon and spinal cord (Fornai et al 1996, Jackisch et al 2008).…”

Section: Discussionmentioning

confidence: 97%

Neurotoxin-Induced DNA Damage is Persistent in SH-SY5Y Cells and LC Neurons

et al. 2015

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Degeneration of the noradrenergic neurons has been reported in the brain of patients suffering from neurodegenerative diseases. However, their pathologic characteristics during the neurodegenerative course and underlying mechanisms remain to be elucidated. In the present study, we used the neurotoxincamptothecin (CPT)to induce the DNA damage response in neuroblastoma SH-SY5Y cells, normal fibroblast cells, and primarily cultured LC and raphe neurons to examine cellular responses and repair capabilities after neurotoxin exposure. To our knowledge, the present study is the first to show that noradrenergic SH-SY5Y cells are more sensitive to CPT-induced DNA damage and deficientin DNA repair, as compared to fibroblast cells. Furthermore, similar to SH-SY5Y cells, primarily cultured LC neurons are more sensitive to CPT-induced DNA damage and show a deficiency in repairing this damage. Moreover, while N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) exposure also results in DNA damage in cultured LC neurons, neither CPT nor DSP4 induce DNA damage in neuronal cultures from the raphe nuclei. Taken together, noradrenergic SH-SY5Y cells and LC neurons are sensitive to CPT-induced DNA damage and exhibit a repair deficiency, providing a mechanistic explanation for the pathologic characteristics of LC degeneration when facing endogenous and environmental DNA-damaging insultsin vivo.

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Section: Discussionmentioning

confidence: 97%

Neurotoxin-Induced DNA Damage is Persistent in SH-SY5Y Cells and LC Neurons

et al. 2015

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Blockade of conditioned avoidance responding by trazodone, etoperidone, and MCPP

1989

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Phenylpiperazines, such as meta-chlorophenylpiperazine (MCPP) a serotonin agonist, have recently been reported to block conditioned avoidance responding (CAR) in the rat, which is an indication of possible antipsychotic utility. Since MCPP is a major metabolite of both antidepressant drugs trazodone (TZ) and etoperidone (ET), both were examined for activity in blocking CAR in a single-trial lever press task in Fisher 344 rats. Both TZ and ET produced dose-related falls in CAR with ED50 values (95% confidence limits) of 13.3 (9.6, 18.5) and 10.4 (8.5, 13.2) mg/kg IP, respectively. In contrast, MCPP had an ED50 value of 2.5 (1.8, 3.6) mg/kg IP TZ, ET, and MCPP were also examined for the production of catalepsy and the blockade of amphetamine-induced stereotypy to determine whether each was acting to block CAR via a dopaminergic mechanism of action. None, however, was found highly active. On the other hand, the serotonin receptor blocker metergoline (1.0 mg/kg IP) significantly reduced the CAR block produced by each, suggesting a serotonergic mechanism of action. Since TZ and ET are both less potent than MCPP, the data also suggest TZ and ET may block CAR via formation of MCPP.

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