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Involvement of central beta-adrenoceptors in the induction of hypothalamic interleukin-1 beta mRNA by methamphetamine
T Yamaguchi1, Y Kuraishi, M Minami
1Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Abstract:
Methamphetamine (2-15 mg/kg, i.p.) has been shown to induce interleukin-1 beta (IL-1 beta) mRNA in the rat hypothalamus. The induction of IL-1 beta mRNA was blocked by intraperitoneal pretreatment with beta-blockers propranolol (0.1-1 mg/kg, but not 0.01 mg/kg) and pindolol (0.3 and 1 mg/kg). Prazosin (1 and 5 mg/kg) and yohimbine (1 and 5 mg/kg), alpha-blockers and haloperidol (1 mg/kg), a dopamine antagonist, produced partial and little suppression, respectively. When injected intracerebroventricularly (i.c.v.), propranolol, but neither prazosin nor yohimbine, significantly suppressed the methamphetamine-induced expression of IL-1 beta mRNA at a dose of 1 nmol/rat. An i.c.v. injection of the beta-adrenoceptor agonist isoproterenol (1 and 3 micrograms/rat) dose-dependently increased the hypothalamic level of IL-1 beta mRNA. The present results suggest that the induction of hypothalamic IL-1 beta mRNA by methamphetamine is mediated by beta-adrenoceptors in the brain.
Insights
Methamphetamine increases interleukin-1 beta (IL-1 beta) mRNA in rat brains. This effect is blocked by beta-blockers, suggesting a role for beta-adrenoceptors in this response.
Area of Science:
- Neuropharmacology
- Molecular Biology
- Neuroinflammation
Background:
- Methamphetamine (MAP) is known to induce interleukin-1 beta (IL-1 beta) mRNA expression in the rat hypothalamus.
- The precise mechanisms underlying this induction are not fully understood.
Purpose of the Study:
- To investigate the role of adrenoceptors in mediating the methamphetamine-induced expression of IL-1 beta mRNA in the rat hypothalamus.
- To determine whether beta-adrenergic pathways are involved in this neuroinflammatory response.
Main Methods:
- Rats were administered methamphetamine (i.p.) and various receptor antagonists or agonists.
- Interleukin-1 beta mRNA levels in the hypothalamus were measured.
- Drugs were administered intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.).
Main Results:
- Intraperitoneal beta-blockers (propranolol, pindolol) significantly blocked methamphetamine-induced IL-1 beta mRNA expression.
- Alpha-blockers (prazosin, yohimbine) and a dopamine antagonist (haloperidol) showed only partial or minimal suppression.
- Intracerebroventricular propranolol suppressed the induction, while prazosin and yohimbine did not.
- Intracerebroventricular isoproterenol (a beta-agonist) dose-dependently increased IL-1 beta mRNA levels.
Conclusions:
- The induction of hypothalamic IL-1 beta mRNA by methamphetamine is primarily mediated by beta-adrenoceptors in the brain.
- Beta-adrenergic pathways play a significant role in the neuroinflammatory response to methamphetamine.