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Psilocybin: biphasic dose-response effects on the acoustic startle reflex in the rat.

The startle reflex was measured in 7 groups of 10 rats each after intraperitoneal injection of saline or 0.25, 0.50, 0.75, 1.0, 2.0, 4.0 or 8.0 mg/kg psilocybin. Low doses (0.75-2.0 mg/kg) increased startle amplitude whereas high doses (4.0-8.0 mg/kg) depressed startle. Selected low (0.71 mg/kg) or high (5.70 mg/kg) doses of psilocin also had a biphasic dose-response effect on startle comparable in magnitude to equimolar doses of psilocybin. This biphasic dose-response relationship of the indole hallucinogen, psilocybin, on startle is consistent with the hypothesis that startle is increased when the firing rates of midbrain raphe neurons are selectively inhibited but is depressed when neurons postsynaptic to raphe cells are also inhibited.

Acoustic Stimulation

Startle reflex habituation in children with cerebral palsy.

Two groups of children (9 with cerebral palsy and 10 normals, matched for sex and age) participated in a study of the startle reflex. Each child was instructed to press a button as soon as possible after the onset of a visual stimulus on a box on the table at which they were seated. During some of the trials, a sudden and intense auditory stimulus (85 dB) was presented concomitantly with the onset of the visual stimulus, and effects on reaction time recorded. Mean reaction time of normal children was significantly faster than that of the group with cerebral palsy. The magnitude of disruption associated with the first startle stimulus presentation was signicantly greater for cerebral palsied children. The course between groups of habituation to the startle stimuli was not significantly different. Data support the hypothesis that startle reflexes of children with cerebral palsy are more marked than are those of normal children.

Acoustic Stimulation

Correlation of the startle reflex and Mauthner cell auditory responses in unrestrained goldfish.

Stainless-steel electrodes were implanted near the left or right. Mauthner cells (M-cells) of goldfish to determine if these cells can initiate the startle reflex evoked by a brief sinusoidal sound stimulus. Recordings of the M-cell extracellular spike were obtained for the duration of 10 experiments. Fish with chronic implants were allowed to free-swim and exposed to at least 10 consecutive sound stimuli consisting of 2 cycles of 200 Hz. Seventy-three startle responses were analysed. In 34 cases the implanted M-cell electrode was contralateral to the contracting musculature, and in each of these cases, a M-cell spike preceded the EMG response by 1-1-2-1 ms. In the reamining 39 cases the electrode was ipsilateral to the active musculature, and the M-cell only fired in one of these trails. There were no startle responses and no M-cell firings in an additional 52 tests. Since the M-cell activates contralateral motoneurones, the results indicate it is responsible for initiation of the startle reflex.

Action Potentials

Tryptophan-free diet: effects on the acoustic startle reflex in rats.

In Experiment 1, body weights of rats fed a powdered tryptophan-free (TF) diet decreased monotonically during a 13-day period. Control animals fed the same diet supplemented with 0.5% L-tryptophan gained weight. The groups did not differ significantly in acoustic startle amplitude measured at 2, 4, 6, 7, 9, 11, and 13 days despite a 28% decrease in whole-brain serotonin in the TF rats. In Experiment 2, daily intubation of rats with a syrup form of each diet maintained the two groups' body weights at comparable levels. TF diet intubation decreased whole-brain serotonin by 64% and produced significantly elevated startle amplitudes, which returned to control levels when 0.5% L-tryptophan was added to the diet. Changes in whole-brain serotonin level preceded changes in startle amplitude by several days. In Experiment 3, acute injections of 125 mg/kg L-tryptophan significantly reduced the startle amplitude of TF diet intubated rats and significantly raised their brain serotonin levels. The results show that acoustic startle reflex is increased by a TF diet, provided the animals receive adequate nourishment, and suggest that this facilitation may result from depletion of brain serotonin.

Acoustic Stimulation

Modulation of the acoustic startle reflex in humans in the absence of anticipatory changes in the middle ear reflex.

If a weak tone precedes an intense tone, then the acoustic startle eyeblink reflex elicited by the stronger stimulus is inhibited. It has been suggested that the leading stimulus gives rise to a protective middle ear reflex that attenuates the effective intensity of the second. This hypothesis was tested and disproved. In seven subjects intense tone bursts sufficient to elicit both intratympanic and eyeblink responses were presented sometimes alone and sometimes preceded at various lead times (25 to 400 msec) by a weak tone. The weak tone inhibited the amplitude of the eye blink to the strong tone, maximally at intervals of 100 to 200 msec, but was never seen to produce any of the anticipatory impedance changes that would be characteristic of middle ear reflex activity during the interval between the two stimuli.

Adolescent

Excitation of the common inhibitory motor neuron: a possible role in the startle reflex of the cockroach, Periplaneta americana.

The responses of the widespread common inhibitory motor neuron (CI) to tactile stimulation of the cercus and the abdomen and electrical stimulation of the cercal nerve and the abdominal connectives are investigated. Tactile stimulation produces high frequency (greater than 500 impulses/s) spike discharge in CI with the onset of CI activity preceding the discharge of the excitatory motor neurons. Electrical stimulation of the connectives demonstrates a monosynaptic connection between at least one intermediate sized fiber (conduction velocity =3.7 m/s) in the abdominal connective and the ipsilateral CIs in the meso-and metathoracic ganglia. Electrical stimulation of the cercal nerve suggests a disynaptic path from cercal nerve to CI. Arguments are presented for a cercal afferent-to-CI reflex and the possible functional role of early excitation of CI is discussed.

Animals

Development of the acoustic startle response in the rat: ontogenetic changes in the magnitude of inhibition by prepulse stimulation.

Three experiments examined the development of the acoustic startle reflex and its modification by a preliminary stimulus in the infant rat during the 2nd and 3rd postnatal weeks. The 1st experiment employed a white noise S1 (20 msec, 70 dB), the 2nd a cutaneous S1 (.5 msec, .5 mA and 1.0 mA shock), and the 3rd identical S1-S2 pairs (20 msec, 10 kHz, 110 dB tones). The results demonstrate a similar maturation of the prepulse modification pattern over days in the 3 experiments, evidenced mainly in the growth of inhibition. The findings indicate peripheral and central mechanisms that are maturing during the period of life under observation and that contribute to the developmental patterns of modification.

Acoustic Stimulation

Functional development in the Mauthner cell system of embryos and larvae of the zebra fish.

In the embryonic zebra fish as early as 40 hr after fertilization, the Mauthner cells (M-cells) initiate an escape response, elicited by tactile-vibrational stimulation. The initial part of this behavior is similar to the acoustic startle reflex seen during the larval stage which begins at 96 hr. The embryonic response is directional and is followed by a series of strong tail flexures which are more pronounced than those during swimming. In the embryo the M-cell fired at the beginning of the response and rarely fired again during subsequent contractions; in our experiments the M-cell did not mediate iterative movements of the tail. The M-cell system is probably involved in evoked hatching behavior, as the tactile response is sufficient to rupture the egg membrane and allow the animal to escape. The M-cell sometimes fired spontaneously, which suggests that it might function also in spontaneous hatching behavior which occurs in the absence of phasic stimulation. At 48 hr the M-cell has morphologically mature synapses on its soma and dendrites, but its cytoplasm is relatively undifferentiated; it has few oriented neurofilaments and no distinct axon hillock. During these stages the extracellular M-spike is longer in duration and smaller in amplitude than at later times when the cell is more mature morphologically. Our data suggest that long-term inhibitory control of the M-cell system begins to function at about the time of hatching. At this time the cell is morphologically mature and is richly supplied with synaptic endings over its soma and dendrites.

Action Potentials

Excitatory and inhibitory components of the eyeblink responses to startle evoking stimuli, studied in the human subject.

Integrated EMG recordings have been used to study the eyeblink component of the human startle reflex. They have shown that the response, to either an auditory or a painful stimulus, consists of an initial excitation followed by a more prolonged period during which a second stimulus, of the same or different sensory modality, fails to evoke a response, or evokes one which is reduced in amplitude. The period of reduced responsiveness does not follow voluntary or spontaneous eyeblinks. Increasing the duration of the startle evoking stimulus has little effect on the excitatory component of the response, but prolongs the subsequent period of reduced responsiveness. When stimuli of one modality are presented repetitively to the subject, the eyeblink response is habituated; the response to a subsequent testing stimulus, of a different sensory modality, is then smaller than that evoked by the testing stimulus alone, but greater than that evoked by the testing stimulus when it follows a single conditioning stimulus. It is concluded that the excitatory and inhibitory components of the startle reflex are at least partially separable and that stimulus novelty has some significance in eliciting a response.

Acoustic Stimulation

Lead-stimulation effects of human cardiac orienting and blink reflexes.

Innocuous prestimulation can inhibit or facilitate a startle reflex in lower animals, depending on its lead time and on whether it is dircrete or continues throughout the lead interval. Similar effects of lead stimulation on the unconditioned blink reflex were found in human subjects, but human subjects also showed an effect not seen in lower animals. Under conditions of temporal and stimulus uncertainty, the presentation of discrete stimuli at lead times that have no effect in rats produced blink facilitation as well as pronounced cardiac decelerations during the lead interval in man. The article suggests that this effect might be mediated by an attentional process and that it could be dissociated from effects produced by a classical arousal mechanism.

Acoustic Stimulation

Involvement of norepinephrine in startle arousal after acute and chronic d-amphetamine administration.

Treatment with d-amphetamine produced a dose-dependent increase in startle amplitude in response to a buzzer. This increase appeared to be a reflection of a sensitization effect, i.e., enhanced responsivity as a function of repeated stimulus presentations. Treatment with alpha-methyl-p-tyrosine, which reduced whole brain concentrations of dopamine (DA) and norepinephrine (NE), or treatment with FLA-63, which reduced only NE, antagonized the effects of d-amphetamine on the startle reflex, suggesting a role of NE in this behavior. Startle amplitude was also reduced following chronic d-amphetamine treatment. The effect of d-amphetamine on startle was found to be independent of changes in drug-induced locomotor excitation. The data of the present investigation, together with earlier reports, suggests that tolerance occurs to those behaviors that involve a noradrenergic component.

Animals

Plasticity of the acoustic startle response in the acutely decerebrate rat.

Plasticity of the acoustic startle reflex was measured in rats in which a complete transection between the forebrain and midbrain was made. During a period from 60 to 100 min after surgery, startle amplitude in the transected rats was relatively stable and comparable with that of the controls (which had been anesthetized with halothane and placed in a stereotaxic instrument). During this period the transection did not alter the temporal recovery process (with intervals of 2, 4, 8, or 16 sec) or auditory prepulse inhibition (with intervals of 25, 50, 100, 500, or 1,000 msec) or the normal reduction in startle caused by high levels of background noise. The transection did prevent the normal increase in startle caused by moderate levels of background noise and eliminated within-session habituation. The effect on habituation was particularly convincing since the curves of the transected and nontransected rats actually crossed. The results are discussed in terms of how the transection procedure can be used to evaluate various hypotheses about underlying mechanisms of startle plasticity.

Acoustic Stimulation

Temporal integration of acoustic stimulation obtained in reflex inhibition in rats and humans.

An acoustic stimulus (S1) presented just before reflex elicitation inhibits reflex expression. The present studies questioned whether inhibition provided by initial stimuli of various durations conforms to established temporal integration functions. Initial stimuli were noise bursts varying in duration (2, 20, or 200 msec) and intensity (55 or 85 dB). Eliciting stimuli (S2) for rats were intense tone bursts, which elicited the acoustic startle reflex, and for humans electrotactile stimuli to the forehead, which elicited the eye blink. Findings revealed that inhibition was greater with the 85-dB S1 stimulus and increased linearly with log increases in duration. These latter data suggest that the acoustic substrate for reflex inhibition has a long-time constant. There was one exception to this general finding. For seven (of nine) human subjects, inhibition declined when the duration of the 85-dB S1 was increased from 20 to 200 msec. Postexperimental questioning and video monitoring suggest that this anomaly resulted from a reflex enhancing arousal process.

Acoustic Stimulation

Reflex activation of laryngeal muscles by sudden induced subglottal pressure changes.

In measuring the effect of subglottal pressure changes on fundamental frequency (Fo) of phonation, the effects of changing laryngeal muscle activity must be eliminated. Several investigators have used a strategy in which pulsatile increases of subglottal pressure are induced by pushing on the chest or abdomen of a phonating subject. Fundamental frequency is then correlated with subglottal pressure changes during an interval before laryngeal response is assumed to occur. The present study was undertaken to repeat such an experiment while monitoring electromyographic (EMG) activity of some laryngeal muscles, to discover empirically the latency of the laryngeal response. The results showed a consistent response to each push, with a latency of about 30 ms. Despite this response, analyses of fundamental frequency versus subglottal pressure changes during the interval of constant EMG activity were in general agreement with previously published values. With respect to the nature of the electromyographic response itself, its timing was found to be within the range of latencies appropriate for peripheral feedback, and was also similar to that for an acoustically--or tactually--elicited startle reflex.

Electromyography