A Stinging Suspicion Something Was Just Not Right: Methamphetamine Toxicity in Infant Mimics Scorpion Envenomation.

The sting from Centuroides sculpturatus, commonly known as the bark scorpion, is a serious medical problem and can be potentially fatal to young children. Centuroides sculpturatus envenomation can cause a wide spectrum of symptoms, often including autonomic dysfunction, cranial nerve abnormalities, and somatic motor abnormalities. We discuss a 6-month-old male infant who presented with signs and symptoms consistent with bark scorpion envenomation, later found to be secondary to methamphetamine toxicity. Emergency pediatricians should be aware of the strong similarities between scorpion envenomation and methamphetamine toxicity in pediatric patients residing in or having visited the southwestern region of the United States. Methamphetamine toxicity should be considered in their differential diagnosis.

Effects of coincident 5-HT1A receptor stimulation and NMDA receptor antagonism on L-DOPA-induced dyskinesia and rotational behaviors in the hemi-parkinsonian rat.

RATIONALE: Serotonin 1A receptor (5-HT1AR) agonists reduce L-DOPA-induced dyskinesia and enhance motor function in experimental and clinical investigations of Parkinson's disease (PD). While the mechanism(s) by which these effects occur are unclear, recent research suggests that modulation of glutamate neurotransmission contributes. OBJECTIVE: To further delineate the relationship between 5-HT1A receptors and glutamate, the current study examined the effects of the 5-HT1AR agonist, +/-8-OH-DPAT and the N-methyl-D-aspartic acid receptor (NMDAR) antagonist, MK-801, on L-DOPA-induced motor behavior. MATERIALS AND METHODS: Unilateral 6-hydroxydopamine lesioned male Sprague-Dawley rats were rendered dyskinetic with 1 week of daily L-DOPA (12 mg/kg, i.p.) + benserazide (15 mg/kg, i.p.). On test days, one group of rats received pretreatments of: +/-8-OH-DPAT (0, 0.03, 0.1, 0.3 mg/kg, i.p.) or MK-801 (0, 0.03, 0.1, 0.3 mg/kg, i.p.). A second group was administered combined +/-8-OH-DPAT (0, 0.03 or 0.1 mg/kg, i.p.) + MK-801 (0, 0.1 mg/kg, i.p.). Pretreatments were followed by L-DOPA administration, after which, abnormal involuntary movements (AIMs) and rotations were monitored. To investigate effects on motor performance, subthreshold doses of +/-8-OH-DPAT (0.03 mg/kg, i.p.) + MK-801 (0.1 mg/kg, i.p.) were administered to L-DOPA-naïve hemiparkinsonian rats before the forepaw adjusting steps test. RESULTS: Individually, both +/-8-OH-DPAT and MK-801 dose-dependently decreased L-DOPA-induced AIMs without affecting rotations. Combined subthreshold doses of +/-8-OH-DPAT+MK-801 reduced L-DOPA-induced AIMs and potently enhanced contralateral rotations without altering L-DOPA-induced motor improvements. CONCLUSIONS: The current results indicate a functional interaction between 5-HT1AR and NMDAR that may improve pharmacological treatment of PD patients.

Serotonin 1B receptor stimulation reduces D1 receptor agonist-induced dyskinesia.

Dopamine replacement therapy for the treatment of Parkinson's disease leads to deleterious abnormal involuntary movements (AIMs), known as L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia, which parallels enhanced striatal dopamine D1 receptor-mediated signaling. Recent evidence suggests stimulation of striatal serotonin (5-HT) 1B receptors may reduce D1-mediated signaling. Given this potential antidyskinetic mechanism, male hemiparkinsonian Sprague-Dawley rats received treatments of D1 receptor agonist, SKF81297, (0.8 mg/kg) or L-DOPA (12 mg/kg, subcutaneous injection). Dyskinetic movements were rated using the AIMs scale. Rats were then administered vehicle (100% dimethyl sulfoxide) or the 5-HT1B receptor agonist, CP94253, (1.5 or 3.0 mg/kg, subcutaneous injection), followed by SKF81297 or L-DOPA and rated for AIMs. Results indicate that CP94253 mitigates both L-DOPA and D1 receptor agonist-induced dyskinesia. These findings suggest that 5-HT1B receptor stimulation directly diminishes D1 receptor-mediated dyskinesia, implicating an important target for the treatment of L-DOPA-induced dyskinesia.