Putative nociceptive neurotransmitters in the mesencephalic reticular formation

The neurotransmitter(s) involved in the transmission of nociceptive information in the mesencephalic reticular formation (MRF) of the rat have not been identified. Acetylcholine (ACh), substance P (SP), neurotensin (NT), norepinephrine (NE) and dopamine (DA) have all been implicated as putative neurotransmitters involved in nociception. All of these compounds were microiontophoretically administered in the MRF of rats to determine which, if any, mimicked the effects produced by a nociceptive stimulus (foot pinch). This is only one of several criteria that a substance should meet to be considered a nociceptive neurotransmitter in the MRF. ACh and NE mimicked the effects of the nociceptive stimulus in 61% and 67% respectively of the cells tested; NT, DA and SP mimicked the effects of the nociceptive stimulus less frequently (33%, 30%, 23% respectively). Therefore, the nociceptive neurotransmitters in the MRF appear to be ACh and NE; NT, DA and SP may be neurotransmitters with a less important role in nociception in the MRF.     

Interactions of morphine with putative neurotransmitters in the mesencephalic reticular formation

Acetylcholine (ACh) and norepinephrine (NE) have been identified previously as putative nociceptive neurotransmitters in the mesencephalic reticular formation (MRF) of the rat because they frequently mimic the change in neuronal firing (usually an increase) evoked by a noxious stimulus (NS). The purpose of this study was to determine if 1.) morphine (M) acts to prevent the increase in firing evoked by a NS by blocking the effects of either of these two neurotransmitters and 2.) if this effect is a specific narcotic effect. Using the technique of microiontophoresis in conjunction with extracellular recording, we located single units in the MRF in which 1.) neuronal firing was accelerated by a NS: 2.) M blocked this response; and 3.) either ACh or NE mimicked the effect of the NS. Neurons meeting these three criteria were studied further to determined if morphine would also block the response to either of the neurotransmitters and if this was a specific narcotic effect. We found that morphine blocked the increase in neuronal firing evoked by the NS and ACh or the NS and NE in over 50% of the cells meeting the above criteria. Some neurons were found in which both ACh and NE mimicked the NS and M blocked all three responses. This blockade of these neurotransmitters was a specific narcotic effect because it could be reversed by the systematic administration of naloxone. These data lead to the tentative hypothesis that M, acting via an opiate receptor, blocks the increase in neuronal firing evoked by a NS by blocking the postsynaptic effects of either ACh or NE. This may be one of the mechanisms by which morphine acts to produce analgesia.     

Involvement of mesencephalic reticular formation neurons in cat conditioned reflexes

Traditional defensive and operant food reflexes were used to investigate neuronal responses of the mesencephalic reticular formation. It was found that these neurons may be divided into different groups according to function, depending on how they respond to positive conditioning stimuli. Of the two main groups of neurons with sustained tonic reactions one is activated in response to positive acoustic conditioning stimulation; it no longer reacts to the same stimulus after extinction of the reflex, while the other only becomes involved in response to positive stimulation accompanying the initiation of movement. Neurons belonging to the second group begin to respond directly to acoustic stimulation after extinction of the conditioned reflex. Neurons of the mesencephalic reticular formation can thus exercise additional tonic ascending effects both in the production and inner inhibition of the conditioned reflex. The group of neurons with a phasic reaction, i.e., a double response (a direct response to sound and another produced by movement) displayed a drop in spontaneous activity during the shaping of inhibition of differentiation and of extinction in particular. It was found that the initial changes in the spike response of reticular formation neurons during conditioning and pseudo-conditioning are similar. There are thus grounds for stating that neurons of the mesencephalic reticular formation participate in the shaping, production, and inner inhibition of traditional and operant conditioned reflexes in a differentiated capacity rather than as a population reacting identically.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 18, No. 2, pp. 161–171, March–April, 1986.     

Steroid anaesthesia: alphadione depresses multiunit activity in the mesencephalic reticular formation

Cortical EEG and multiunit activity (MUA) of the mesencephalic reticular formation (MRF), area hypothalami anterior (AH) and the nucleus amygdalae basalis (AMY) were studied before and after different doses of alphadione (Althesin) and hexobarbitone (Evipan-Natrium) given to cats with chronically implanted electrodes. Non-anaesthetic doses of alphadione (0.15 ml/kg; 0.3 ml/kg; 0.6 ml/kg and 1.2 ml/kg i.p.) had sedative effects decreasing selectively the MUA in the MRF. In doses of 2.0 ml/kg, 2.4 ml/kg and 3.0 ml/kg i.p., alphadione induced anaesthesia which was associated with a rapid decrease of MUA in the MRF and by a gradual decrease of activity in the AH and AMY. The i.p. dose of 3.0 ml/kg abolished MUA responses of the reticular formation to acoustic, visual and somatic stimulation but failed to block responses to pain. Deep anaesthesia with lasting analgesia could be maintained by i.v. infusion (0.075 ml/kg/min). This procedure blocked the responsiveness to painful stimulation while pharyngeal and laryngeal reflexes were maintained. Hexobarbitone in a dose of 20.0 mg/kg i.p. did not produce anaesthesia in the cat. Administration of 40.0 mg/kg i.p. resulted in a rapid decrease of MUA in the MRF, AH and AMY, MUA responses to each stimulation were abolished and the pharyngeal reflex was blocked.     

Temporal patterns of unit activity of mesencephalic reticular nuclei during sleep and waking

Temporal patterns of unit activity in the mesencephalic reticular nuclei (n. cuneiformis, n. parabrachialis) were studied in unrestrained rats during the sleep-waking cycle; activity was derived by means of movable metallic microelectrodes. Analysis of the data showed that most neurons of these mesencephalic reticular nuclei (76 and 66% respectively) generate activity with the highest frequency during active waking and the emotional stage of paradoxical sleep; they discharge with lower frequency during passive wakefulness and the nonemotional stage of paradoxical sleep, and they exhibit least activity during slow-wave sleep. Comparatively few neurons (24 and 15%) demonstrate the opposite kind of temporal pattern of activity: They discharge more intensively during slow-wave sleep and more slowly during active wakefulness and the emotional stage of paradoxical sleep. Activity of these neurons during quiet wakefulness and the nonemotional stage of paradoxical sleep reaches the level of activity observed during slow-wave sleep. Neurons discharging intensively during active wakefulness were found in n. parabrachialis; their discharge frequency during passive wakefulness and slow-wave sleep and its frequency was least during paradoxical sleep. The similarity and differences of the neurophysiological mechanisms of regulation of the phases and stages of the sleepwaking cycle are discussed.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 16, No. 5, pp. 678–690, September–October, 1984.     

Cytophotometric analyses of mesencephalic reticular formation neuronal RNA in soman intoxicated rats

Quantitative azure B cytophotometry was used to monitor ribonucleic acid (RNA) responses of individual neurons within the nucleus cuneiformis (NC) and ventrotegmental nucleus (VTN) of the rat mesencephalic reticular formation following single subcutaneous soman (pinacolyl methylphosphonofluoridate) injections (0.5, 0.9 or 1.5 LD₅₀). The sub-lethal (0.5 LD₅₀) dosage of soman produced RNA accumulation in NC neurons, but VTN-RNA levels were not significantly altered. In contrast, both reticular nuclei exhibited prominent RNA depletion with higher soman dosages, the severity of which was greater with lethal (1.5 LD₅₀) than near-lethal (0.9 LD₅₀) dosages. These data indicate that metabolic correlates of enhanced activation of cholinergic reticular nuclei are present only with sub-lethal dosages, and that higher dosages produce characteristics of impaired activation of ascending cholinergic pathways. At present, mechanisms underlying soman-induced metabolic and neurologic deficits remain speculative.     

Participation of the thalamic reticular nucleus in the shaping of the interrelations of the mesencephalic reticular formation and the lateral geniculate body

On the awake rabbits and cats under nembutal anesthesia it has been shown that the reticular nucleus of the thalamus takes considerable part in the formation of reticulogeniculate response of the lateral geniculate body (LGB) to electrostimulation of the mesencephalic reticular formation. It is assumed that the reticular nucleus of the thalamus takes basic part in a realization of "rapid" physical influences of the reticular formation on the LGB.