Laryngeal adductor responses to afferent stimulation play a key role in airway protection. Although vital for protection during cough and swallow, these responses also must be centrally controlled to prevent airway obstruction by laryngospasm during prolonged stimulation. Our purpose was to determine the role of N-methyl-D-aspartate (NMDA) receptors in modulating early R1 responses (at 9 ms) and/or later more prolonged R2 responses (at 36 ms) during electrical stimulation of the laryngeal afferent fibers contained in the internal branch of the superior laryngeal nerve in the cat. The percent occurrence, amplitude, and conditioning of muscle responses to single superior laryngeal nerve (SLN) stimuli presented in pairs at interstimulus intervals of 250 ms were measured in three experiments: 1) animals that had ketamine as anesthetic premedication were compared with those who did not, when both were maintained under alpha-chloralose anesthesia. 2) The effects of administering ketamine in one group of animals were compared with increasing the depth of alpha-chloralose anesthesia without NMDA receptor blockade in another group of animals. 3) The effects of dextromethorphan (without anesthetic effects) were examined in another group of animals. In the first experiment, the occurrence of R2 responses were reduced from 95% in animals without ketamine premedication to 25% in animals with ketamine premedication (P = 0.015). No differences occurred in the occurrence, amplitude, latency, or conditioning effects on R1 responses between these groups. In the second experiment, the occurrence of R2 responses was reduced from 96 to 79% after an increase in the depth of anesthesia with alpha-chloralose in contrast with reductions in R2 occurrence from 98 to 19% following the administration of ketamine to induce NMDA receptor blockade along with increased anesthesia (P = 0.025). In the third experiment, R2 occurrence was reduced from 89 to 27% (P = 0.017) with administration of dextromethorphan while R1 response occurrence and amplitude did not change. In each of these experiments, NMDA receptor blockade did not have significant effects on cardiac or respiratory rates in any of the animals. The results demonstrate that NMDA receptors play an essential role in long latency R2 laryngeal responses to laryngeal afferent stimulation. On the other hand, early R1 laryngeal adductor responses are likely to involve non-NMDA receptor activation.

The cardinal motor symptoms of Parkinson's disease (PD) include resting tremor, akinesia, bradykinesia, and rigidity, and these motor abnormalities can be modeled in rodents by administration of the VMAT-2 (type-2 vesicular monoamine transporter) inhibitor tetrabenazine (9,10-dimethoxy-3-(2-methylpropyl)-1,3,4,6,7, 11b hexahydrobenzo[a]quinolizin-2-one; TBZ). Depression is also commonly associated with PD, and clinical data indicate that selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine ((±)-N-methyl-γ-[4-(trifluoromethyl)phenoxy]benzenepropanamine hydrochloride; FLX) are frequently used to treat depression in PD patients. The aim of the present study was to characterize the effect of FLX on the motor dysfunctions induced by a low dose of TBZ (0.75 mg/kg), and investigate the neural mechanisms involved. This low dose of TBZ was selected based on studies with rat models of depressive symptoms. In rats, coadministration of FLX (2.5, 5.0, and 10.0 mg/kg) increased TBZ-induced oral tremor (tremulous jaw movements), and decreased locomotor activity compared with administration of TBZ alone. Coadministration of the serotonin 5-HT2A/2C antagonist mianserin (2.5 and 5.0 mg/kg) attenuated the increase in oral tremor induced by coadministration of TBZ (0.75 mg/kg) with FLX (5.0 mg/kg). Consistent with these behavioral data, coadministration of TBZ and FLX decreased DA tissue levels in the rat ventrolateral neostriatum compared with TBZ alone, and coadministration of mianserin with TBZ and FLX attenuated this effect, increasing DA tissue levels compared with the TBZ/FLX condition. These data suggest that SSRI administration in PD patients may result in worsening of motor symptoms, at least in part, by exacerbating existing DA depletions through 5-HT2A/2C-mediated modulation of DA neurotransmission.