Effects of low-doses of methamphetamine on d-fenfluramine-induced head-twitch response (HTR) in mice during ageing and c-fos expression in the prefrontal cortex.

BACKGROUND: The head-twitch response (HTR) in mice is considered a behavioral model for hallucinogens and serotonin 5-HT2A receptor function, as well as Tourette syndrome in humans. It is mediated by 5-HT2A receptor agonists such as ( ±)- 2,5-dimethoxy-4-iodoamphetamine (DOI) in the prefrontal cortex (PFC). The 5-HT2A antagonist EMD 281014, can prevent both DOI-induced HTR during ageing and c-fos expression in different regions of PFC. Moreover, the nonselective monoamine releaser methamphetamine (MA) suppressed DOI-induced HTR through ageing via concomitant activation of inhibitory 5-HT1A receptors, but enhanced DOI-evoked c-fos expression. d-Fenfluramine is a selective 5-HT releaser and induces HTR in mice, whereas MA does not. Currently, we investigated whether EMD 281014 or MA would alter: (1) d-fenfluramine-induced HTR frequency in 20-, 30- and 60-day old mice, (2) d-fenfluramine-evoked c-fos expression in PFC, and (3) whether blockade of inhibitory serotonergic 5-HT1A- or adrenergic ɑ2-receptors would prevent suppressive effect of MA on d-fenfluramine-induced HTR. RESULTS: EMD 281014 (0.001-0.05 mg/kg) or MA (0.1-5 mg/kg) blocked d-fenfluramine-induced HTR dose-dependently during ageing. The 5-HT1A antagonist WAY 100635 countered the inhibitory effect of MA on d-fenfluramine-induced HTR in 30-day old mice, whereas the adrenergic ɑ2 antagonist RS 79948 reversed MA's inhibitory effect in both 20- and 30- day old mice. d-Fenfluramine significantly increased c-fos expressions in PFC regions. MA (1 mg/kg) pretreatment significantly increased d-fenfluramine-evoked c-fos expression in different regions of PFC. EMD 281014 (0.05 mg/kg) failed to prevent d-fenfluramine-induced c-fos expression, but significantly increased it in one PFC region (PrL at - 2.68 mm). CONCLUSION: EMD 281014 suppressed d-fenfluramine-induced HTR but failed to prevent d-fenfluramine-evoked c-fos expression which suggest involvement of additional serotonergic receptors in the mediation of evoked c-fos. The suppressive effect of MA on d-fenfluramine-evoked HTR is due to well-recognized functional interactions between stimulatory 5-HT2A- and the inhibitory 5-HT1A- and ɑ2-receptors. MA-evoked increases in c-fos expression in PFC regions are due to the activation of diverse monoaminergic receptors through increased synaptic concentrations of 5-HT, NE and/or DA, which may also account for the additive effect of MA on d-fenfluramine-evoked changes in c-fos expression. Our findings suggest potential drug receptor functional interaction during development when used in combination.

Idiopathic intracranial hypertension associated with polycystic ovarian syndrome, sensorineural hearing loss, and elevated inflammatory markers that lead to bilateral blindness: A case report with literature review.

Background: Pseudotumor cerebri (PTC) or idiopathic intracranial hypertension (IIH) is characterized by elevated intracranial pressure without hydrocephalus or mass lesion, with normal cerebrospinal fluid (CSF) studies and neuroimaging. The exact cause remains uncertain, but potential mechanisms include increased CSF production, impaired CSF absorption, cerebral edema, and abnormal cerebral venous pressure gradients. Patients may present with various accompanying symptoms such as unilateral or bilateral visual obscuration, pulsatile tinnitus, back pain, dizziness, neck pain, blurred vision, cognitive difficulties, radicular pain, and typically intermittent horizontal diplopia. Case Description: We report a case of a 32-year-old female who initially presented with chronic headaches and oligomenorrhea, which resulted in the diagnosis of polycystic ovary syndrome (PCOS) a few years before the initial diagnosis of PTC. Despite receiving maximum medical treatment and undergoing optic nerve sheath fenestration, the patient experienced complete bilateral vision loss. Nearly 5 years later, the patient sought care at our outpatient neurology clinic, presenting with symptoms including tinnitus, left-sided hearing loss, and joint pain with elevated inflammatory markers and headaches. The focus of this research was to discuss the pathophysiology of each of these comorbidities. Conclusion: This case report aims to explore the pathophysiological relationships between PTC and concurrent comorbidities, including PCOS, sensorineural hearing loss, empty sella (ES) syndrome, and elevated inflammatory markers. Remarkably, no other PTC case with this unique constellation of concurrent comorbidities have been reported in existing medical literature. The case report underscores the critical importance of early diagnosis of IIH and prompt medical intervention, particularly in patients with PCOS experiencing chronic headaches.