Luis A. Marco

Serotonin-containing axon terminals in the hypoglossal nucleus of the rat. An immuno-electronmicroscopic study

The morphology and distribution of serotonin-containing axon terminals in the rat hypoglossal nucleus (XII) was investigated immunocytochemically at the electron microscopic level. Serotonin-positive profiles were found throughout all regions of XII and included unmyelinated axons, varicosities and axon terminals. Most labeled profiles (68.1%) were nonsynaptic unmyelinated axons and varicosities, while synaptic profiles, ending on dendrites and somata, were seen less frequently (28.7%). The majority of labeled axon terminals (76.9%) ended on small-to-medium-sized dendrites. Most axodendritic terminals contained small, round agranular vesicles (20-55 microns), several large (60-100 microns) dense core vesicles, and were associated with a pronounced asymmetric postsynaptic specialization. By contrast, labeled axosomatic terminals were seen less often than those ending on dendrites (23.0%). Axosomatic terminals typically contained small, round, agranular and large dense core vesicles and were associated with a symmetric or no postsynaptic specialization. These results provide the structural substrates for elucidating the functional role of serotonin in tongue control.

Differential distribution of biogenic amines in the hypoglossal nucleus of the rat

SummaryThe distribution of biogenic amines in the rat hypoglossal nucleus (nXII) was investigated with immunocytochemical methods using antibodies to tyrosine hydroxylase (TH) as a marker for catecholamines, and to 5-hydroxytryptamine (5-HT), the principal indoleamine, at the light microscopic level. TH and 5-HT immunoreactivity were found throughout all regions of nXII. Although the innervations overlapped, clearly differnt patterns of distribution were observed. TH immunoreactivity was localized primarily in the ventromedial quadrant of the caudal half of nXII and appeared largely as perisomatic-like profiles. In contrast, 5-HT immunoreactivity was greatest dorsally along the caudal half of nXII, although secondary foci of staining were evident ventrolaterally and, to a lesser extent, ventromedially. A perisomatic-like pattern of termination was observed for 5-HT in both dorsal and ventral regions of nXII. Since ventral and dorsal districts of nXII contain motoneurons that innervate protrusor and retrusor tongue muscles, respectively, we propose that the overlapping, yet differential distributions of catecholamines and indoleamines are important in controlling the relationships between functionally related groups of nXII motoneurons. These findings are discussed in relation to oro-lingual motor dysfunction.

Interconnections between substantia Nigra reticulata and medullary reticular formation

Injections of wheat germ agglutinin-HRP into the medullary reticular formation (MRf) or the substantia nigra reticulata (SNr) revealed the presence of reciprocating fiber connections between the two areas. Large injections in the MRf demonstrated the existence of labeled neurons in the lateral portions of the SNr. Isolated injections into the parvocellular nuclei of the MRf resulted in the presence of terminal fields in the SNr particularly its lateral portions. Injections in the SNr resulted in the presence of labeled cells in the parvocellular nuclei. The significance of these findings is discussed in terms of oro-facial dyskinesias.

Ketamine as a pharmacological model for tongue dyskinesia

The purpose of this article is to document that ketamine hydrochloride, administered at an anesthetic dosage of about 100 mg/kg, produces tongue contractile activity in the rat. The methods for monitoring and quantitating ketamine-induced tongue contractions (KITCs) are described. We also found that neuroleptic agents consistently and readily abolish KITCs. On the basis of these observations and other pharmacological properties of ketamine, we propose that KITCs may be a useful model for studying neuroleptic-induced oral dyskinesia, e.g., tardive dyskinesia. Additional findings in support of this model are presented.

Ketamine-induced tongue protrusions in rats

1. The purpose of this study was to demonstrate that ketamine anesthesia (100 mg/kg) induces tongue protrusions (P) in addition to retrusions (R) and swallows (S) in adult rats. 2. These linguo-pharyngeal events occur alone or combined in various sequential patterns. 3. The SPR sequence is not the predominant pattern in all preparations suggesting profound disruption of physiological linkages by ketamine. 4. Haloperidol administration suppresses these events for 1-120 min depending on the dose (0.75-2.5 mg/kg). 5. Swallows are the least vulnerable to haloperidol. 6. This and previous findings provide further evidence that ketamine induced linguo-pharyngeal activity can serve as a model for acute or tardive dyskinesia better than stereotypies.

Neuroleptic Malignant Syndrome and Severe Thrombocytopenia: Case Report and Literature Review

We report an unusual case of thrombocytopenia associated with neuroleptic malignant syndrome (NMS). A 31-year-old Black male with a history of hypertension, partial seizures, and schizophrenia developed acute rigidity closely followed by severe hyperpyrexia (temperature 102 degree F), tachypnea, and tachycardia. His home medications at the time of presentation included propanolol 10 mg tid, haloperidol 10 mg bid, sodium valproate 500 mg bid, benztropine 1 mg bid, and haloperidol decanoate 100 mg i.m. every 3 weeks, from another psychiatric facility. Despite vigorous therapy for the hyperthermia, he rapidly developed significant hypoxia requiring mechanical ventilation. A diagnosis of neuroleptic malignant syndrome was made and the patient continued to receive aggressive supportive care. On hospital day 2 his platelet count dropped to 47,000/microl and bottomed out at 36,000/microl by day 3 with other blood cell counts remaining within normal limits. Over the next few days he showed rapid clinical improvement with normalization of his blood chemistries and he was discharged home after 5 days of hospitalization in good condition.

Effects of cholinergic and anticholinergic drugs on ketamine-induced linguopharyngeal motor activity

Benztropine mesylate (Cogentin) and physostigmine salicylate (Antilirium), were tested for changes in tongue protrusions, retrusions, and swallowing acts in rats anesthetized with a 100 mg/kg IM injection of ketamine hydrochloride. These ketamine-induced linguopharyngeal events were monitored by means of a force displacement transducer fed onto a polygraph. Benztropine (0.05–1 mg/kg) caused mild to moderate reductions in the rate of these events for a short period of time, up to about 30 min. With physostigmine (5–25 μg/kg), linguopharyngeal activity was markedly increased, up to 50-fold by the highest dose within 5 min and returned almost to the baseline within 60 min. With lower doses, more moderate responses were obtained. If methscopolamine (1.4, 3, 6 mg/kg IM) preceded physostigmine, the physostigmine enhancement was preserved.

Effects of MK-801, a non-competitive NMDA antagonist, on linguopharyngeal events in rats.

The effects of MK-801 at doses from 0.005 to 1 mg/kg IP on linguopharyngeal events (protrusions, retrusions and swallows) were determined in rats to find out whether MK-801 resembles ketamine in its capacity to increase the frequency of recurrence of such events that we have demonstrated in previous studies. All rats receiving a dose of 0.05 mg/kg or higher showed an increase in linguopharyngeal event frequency within 5 min and this enhancement (3-fold from baseline level) was maintained for longer than 1 h. At the lowest dose of 5 µg/kg the effect lasted only very briefly. A general increase in motor behavior was also observed within 10 min of drug administration. More complex patterns of motor behavior, consisting of stereotypical head bobbing, paw movements reminiscent of walking activity, nystagmus, and ataxia were observed with doses of 0.25 mg/kg and higher. All rats showed a marked startle response at early stages post-injection and hypersensitivity to external stimuli such as noise or movement in the room. However, there was an absolute lack of coordinated avoidance responses normally associated with such startle responses or arousing stimuli.

Effects of clozapine on ketamine-induced linguopharyngeal events in rats

We tested the effects of clozapine (0.02-20 mg/kg i.p.) on ketamine-induced linguopharyngeal events in rats anesthetized with i.m. injections of ketamine hydrochloride (100 mg/kg) and mounted on a stereotaxic with the tip of the tongue tied to a force displacement transducer monitoring tongue protrusions, retrusions and swallows. Reduction began at the 0.04 mg/kg dose. At 4.8 mg/kg there was total suppression of events. At 20 mg/kg, suppression lasted for 1 h. Notably clozapine doses causing total suppression of events in our model were much lower than those usually reported to alter dopamine turnover.

CORTICAL CONTROL OF TONGUE CONTRACTILITY IN THE RAT UNDER KETAMINE ANAESTHESIA

1. Cortico‐lingual and linguo‐cortical interconnectivity was investigated in ketamine‐anaesthetized rats mounted onto a stereotaxic apparatus. The tip of the tongue was tied to a force displacement transducer to monitor tongue retrusions. The tongue cortical area was exposed in one or both hemispheres to record evoked potentials or spontaneous electroencephalographic (EEG) activity, or to stimulate electrically with single square pulses of up to 50 V and 0.25 ms pulse width.