Orexinergic neurotransmission in temperature responses to amphetamines
Autor: | Patrick Tan, Daniel Y. Fu, Dmitry V. Zaretsky, Maria V. Zaretskaia, Yaroslav I. Molkov |
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Rok vydání: | 2013 |
Předmět: |
Hyperthermia
General Neuroscience 05 social sciences Antagonist Meth Methamphetamine Pharmacology medicine.disease Serotonergic Orexin receptor 3. Good health 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine chemistry Poster Presentation medicine 0501 psychology and cognitive sciences 050102 behavioral science & comparative psychology Orexin antagonist Amphetamine 030217 neurology & neurosurgery medicine.drug |
Zdroj: | BMC Neuroscience |
ISSN: | 1471-2202 |
Popis: | Derivatives of amphetamines are widely abused all over the world. After long-term use cognitive, neurophysiological, and neuroanatomical deficits have been reported. Neurophysiological deficits are enhanced by hyperthermia, which itself is major mortality factor in drug abusers. Temperature responses to injections of methamphetamine are multiphasic and include both hypothermic and hyperthermic phases, which are highly dependent on ambient temperature and previous exposure to the drug. Also, amphetamine derivatives differentially affect various neuromediator systems, such as dopaminergic, noradrenergic, serotonergic. Finally, body temperature is dependent on multiple thermoregulatory mechanisms and complex neuronal circuitry. Temperature responses to methamphetamine (Meth) at room temperature have non-trivial dose-dependence, which is far from being understood. Intermediate doses of Meth cause less hyperthermia than both low and high doses of the drug. Also, maxima of all responses have different latency: responses to low and high doses are virtually immediate, while a response to an intermediate dose appears to be delayed. In our previous modeling study we demonstrated that such dose-dependence can be explained by interaction of inhibitory and excitatory drives induced by Meth [1]. Recently, we have published data on the involvement of orexinergic neurotransmission in Meth-induced temperature responses [2] where the low dose (10 mg/kg, i.p.) of SB-334867, an antagonist of the first type of orexin receptors (ORX1), was injected 30 min prior to various doses of Meth. While this dose of antagonist clearly suppressed the response to low (1 mg/kg) and intermediate (5 mg/kg) doses of Meth, the effect was statistically significant only at the late phase (t>60 min) of the response to intermediate dose. At the early phase (t |
Databáze: | OpenAIRE |
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