The effect of electroconvulsive shock on the brain stem auditory evoked potential in the rat

Brief Reports

BIOL PSYCHIATRY 1986;21:1327-1331

1327

The Effect of Electroconvulsive Shock on the Brain Stem Auditory Evoked Potential in the Rat N. A. Shaw

Introduction The brain stem auditory evoked potential (BAEP) is a far-field reflection of activity arising principally from the eighth nerve plus the auditory pathways of the brain stem and the mesencephalon. Although originally described in the cat and rat, the BAEP is now recognized to have a valuable role in the detection of hearing loss and the investigation of a range of neurological diseases (Chiappa and Ropper 1982), and possibly in the assessment of psychiatric disorders (Hayashida et al. 1986). The observation by Weiner et al. that BAEPs recorded from psychiatric patients are resistant to the acute effects of electroconvulsive shock (ECS) reinforces the notion that this potential is not readily susceptible to disruption or alteration (Weiner et al. 1981). However, this finding cannot be accepted without qualification. It is possible that the shortacting barbiturate anesthetic and other medication employed to modify ECS treatments could have played a protective role with respect to the evoked potential, or otherwise confounded the results (Weiner 1984). In addition, l-2 min were required to obtain an initial recording during the ictal phase immediately after ECS, thereby potentially masking some very transient abnormality in the waveform. In the present study,

Prom the Department of Physiology, School of Medicine, University of Auckland, Auckland, New Zealand. Supported by the Medical Research Council of New Zealand. Address reprint requests to Dr. N. A. Shaw, Department of Clinical Neurophysiology, Auckland Hospital, Auckland 1, New Zealand. Received April 28, 1986: revised June 2, 1986.

0 1986 Society of Biological

Psychtatry

an attempt was made to replicate and overcome the limitations of the Weiner study by using rats as subjects in which generalized seizure activity was induced while animals were immobilized with curare but not anesthetized.

Methods Subjects were 12 adult male rats (390-520 g). About 10 days prior to the experiment, each animal had a stainless steel skull screw inserted at the vertex while under pentobarbital anesthesia. The vertex appears to be the optimum position from which to record the BAEP in the rat (Shaw 1986a). On the experimental day, the awake animal was initially curarized and artificially ventilated, but no other medication was given. The technique of inducing neuromuscular paralysis in the absence of anesthesia has been previously described, along with the ethical considerations (Shaw 1985). BAEPs were recorded using a Medelec MS6, following stimulation of the ear with 0.1-msec duration rarefaction clicks. Stimulus repetition rate was lO/sec and click intensity was 128 dB peSPL. The bandpass of the amplifiers was lOO-3.2KHz, and the sampling interval was 10 psec. Each epoch of the electroencephalogram (EEG) averaged was 5 msec in duration, starting from stimulus onset. Stimulating and recording conditions were almost identical to those described in a previous report (Shaw 1986a). The principal difference was that in the current study, each BAEP was the average of only 128 responses. ECS (80 mA for 600 msec) was also

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of identical

magnitude

and duration

to that ad-

when its effects on the cortical and cervical SEP of the rat were investigated (Shaw ministered

1985, 1986b).

Seizure

activity

in the EEG was

not monitored.

Results A baseline application

BAEP was recorded just before the of ECS. The first post-ECS record-

ing was made at about I5 set, 1 mitt, and subsequent BAEPs I-min intervals until 10 min. rat consists of four principal

( 1.27

) II

( 0.57 BEFORE ECS

-_A

) I p

a second at about were recorded at The BAEP in the components (or

( 2.03 III p

waves). These are identitied in the baseline rc cording (before ECS) in Figure I. An example of the BAEP

recorded

at intervals

during

the

shown iti Figure I No obvious change in latency, am plitude, or waveform can be discerned. even during the ictal period t 15 SW). This absenct of any effect of the ECS ih confirmed by the group data for the latencies and amplitudes 01 the four waves, which are presented in Figure _. ’ Paired f-tests between the baseline and the IS-set post-ECS BAEPs revealed no signifcanr differences for either the latencics or amplitudes of any of the four waves. Any small fluctuation> first

I(1 min following

ECS

is also

1 IV ( 2.80

)

i“‘;J e:

4 MIN

0.60 ,/\

1.29 i\ il

2.03

b

+ CM

15 SEC

1 MIN

2 MIN

10 MIN

;

+ 10

pv

-J 0.5

M&C

Figure 1. An example of the effects of electroconvulsive shock (ECS) on the brain stem auditory evoked potential (BAEP) recorded from the vertex following monaural click stimulation at a rate of lO/sec. The baseline potential was recorded just before the induction of seizure activity. Subsequent BAEPs were recorded at the times indicated after ECS. In the baseline example, the four major components of the BAEP arc labeled 1, II, III, and IV, with the actual latency (msec) in parentheses. In the remaining BAEPs, only the latencies are indicated. CM identifies the cochlear microphonic potential from which all latencies were calculated. Amplitudes of each wave were calculated by referring them to the subsequent negative trough. Note that BAEPs recorded at 3, 5, 7, and 9 min are not illustrated.

Brief Reports

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BIOL PSYCHIATRY 1986:21:1327-1331

WAVE

I I

I

1 I I t 0

BEFORE

i

I

1

1

1 WAVE

II

WAVE

IV

1

I

WAVE

1

2

ECS

3

4

TIME

AFTER

5

6

t

6

i

f

+

III

i

f

#

I)

#

#

cc

#

+

*

#

6

7

a

WAVE

.25

1

2

Figure 2. Mean ampii&ude (tr indicated after ECS.

3 TIME

SEM)

4

5

AFTER

and latency ( 2

4

II *

WAVE

EC6

10

IV

f

BEFORE

9

>

WAVE

O.OL

I

7

ECS(MIN

WAVE

+

I

I 1I I

T

.25

Ill

I

I

9

10

ECS f MIN f

SD)

of the four BAEP waves at the times

in amplitude following ECS were probably duo to attenuated convulsive movements causing displacement of the plastic tube in thtl car through which the stimulus was delivered

Discussion The present set of data, collected under more rigorously controlled conditions than were possible using human subjects. nonetheless confirms the original report (Weiner et al. 198 I ). As only a comparatively small number of responses had to be averaged in order to obtain good quality BAEPs. initial recordings could be completed soon after the induction of the seizure. However, even during the immediate postECS period, no alteration in the waveform could be detected. A number of studies have now examined the acute effects of ECS on evoked potentials in both animals and humans (Kriss et al. 1980a,b; Weiner et al. 1981; Myslobodsky and Kofman 1982: Shaw 1985. 1986b). A tentative conclusion appears to be that cortically generated potentials are much more vulnerable than those arising in more caudal locations. The current results are consistent with this hypothesis. as the latest of the major components 01 the BAEP waveform probably does not reflect activity much beyond the inferior colliculus (Chiappa and Ropper 1982). Although the BAEP seems to be immune to a standard dose of ECS, other agents can markedly alter its waveform. Among them is the barbiturate anesthetic pentobarbital. where even a moderate surgical dose will produce significant increases in the latencies of all the components in the rat BAEP. as well as complex changes in the amplitudes of the individual waves (Shaw 1986a). Much higher doses will eventually abolish the rat BAEP entirely (Shapiro et al. 1984). As no comparable phenomena were observed following ECS, this might suggest that ECS and barbiturate anesthesia act via quite different mechanisms. The site of action of the latter is generally considered to be inhibition or depression of synaptic transmission (Shapiro et al. 1984). This implies that the acute effects of

N‘S are not mediated by a disruption of synaptic function. but instead may precipitate interitig encc with electrotonic spread (Shaw 1985). In the present study. BAEPI; were recorded following only a single discrete ECS trial i[ cannot be assumed. however. as Weiner ct c&l t 198 1) have pointed out, that an extended period of seizure activity would not significantly motiify the BAEP waveform. Similarly. the rchults should be extrapolated with caution when mu/tiple ECS treatments have been administered Under these circumstances. the complex changes in synaptic function and morphology that OCCUIover time and may partially underlie the thet apeutic efticacy of ECS (Weiricr 1984) might well produce alterations in the BAEP waveform

References Chiappa KH, Kopper AH ( 1982): Evoked potentials in clinical medicine. N EnglJMe~l306:1140-I

150.

Hayashida Y. Mitani Y. Hosoml H. Amemiya M, Mifune K. Tomita S ( 1986): Auditory brainstem responses in relation to the clinical symptoms of schizophrenia. Bid P.sychirrt~ 21: 377-188. Kriss A, Halliday AM, Halliday E, Pratt RTC ( 1980a): Evoked potentials following unilateral ECT. I ‘The somatosensory evoked potential. Elec,trortlcephalogr

Ciitz Neuroph~siol

48:48

l-489.

Kriss A, Halliday AM, Halliday E. Pratt RTC ( 198Ob~: Evoked potentials following unilateral ECT. II. The flash evoked potential, I:/ec,trorncephaloSr c’lin Neurophysiol 48:490-W I Myslobodsky MS. Kofman 0 (1982): Unilateral WI sus bilateral elcctroconvulsivc shock in albino rath: Comparison of behavioral symptomatology and neocortical reactivity changes. Bid Psychicr~1 17:x&3x0. Shapiro SM, Moller AR, Shiu GK (1984): Brainstem auditory evoked potentials in rats with high-doxc pentobarbital, ElPc,troenc~rphm/ol:r Clitz Nmnphysiol

58:266-276.

Shaw NA (1985): Effect of electroconvulsivc shock on the somatosensory evoked potential in the rat. E,Y[J

Neural

90566-579.

Shaw NA ( 1986a): The effect of pentobarbital on the auditory evoked response in the brainstem of the rat. Npltrctph”r”“(.O/‘t~~ 25:63 -70.

BIOL PSYCHIATRY 1986;21:1327-1331

Brief Reports

Shaw NA (1986b): Effect of electroconvulsive shock on the cervical evoked potential in the rat. Exp Neurol9 1&M-649. Weiner RD (1984): Does electroconvulsive therapy cause brain damage? Behav Bruin Sci 7: l-53.

1331

Weiner RD, Erwin CW, Weber BA (1981): Acute effects of electroconvulsive therapy on brainstem auditory-evoked potentials. Electroencephalogr Clin Neurophysiol 52:202-204.

The Effects of Mianserin Therapy on Plasma Renin Activity in Depressed Patients Alfred0 C. Altamura,

Silvio R. Bareggi, Giordano Invernizzi,

Albert0 Morganti, and Albert0 Zanchetti

Introduction The monoamine hypothesis of depression postulates a lack of norepinephrine (NE) and/or serotonin in the central nervous system (CNS) (Schildkraut 1965; Coppen 1967). There are several findings in experimental animals and in patients that support the theory (Maas 1975). For example, tricyclic antidepressants, which inhibit neuronal reuptake of monoamines and thereby potentiate their activity, are effective for treatment of depression (Iversen and Mackay 1979). Several biochemical studies of urinary or cerebrospinal fluid (CSF) levels of NE metabolites have provided direct support for these theories, as well as some rationale for a biochemical subdivision, or for the prediction of therapeutic responsiveness of depressed patients

From the Departments of Clinical Psychiatry (A.C.A. G.I.), Pharmacology (S.R.B), and Clinical Medicine (A.M., A.Z.), Universita’ degli Studi, Milan, Italy. Address reprint requests to Dr. Alfred0 C. Altamura, Department of Clinical Psychiatry. Policlinico, V. F. Sforza 35. 20122 Milan, Italy. Received October 18, 1985; revised June 4, 1986.

0 1986 Society of Biological

Psychiatry

(Mass et al. 1972; Mass 1975). These have been based on the assumption that CSF and/or urinary levels of NE metabolites might be indices of the metabolism of this amine (Mass et al. 1972; Mass 1975) However, these approaches raise ethical and interpretative problems, and there is therefore a continuing search for other biochemical markers that can demonstrate subgroups of endogenous depression with impaired NE function and prove that antidepressants can modify the activity of the noradrenergic system. It is known that the sympathetic system influences renin release and that this control is centrally organized, as stimulation of the defense area in the lateral hypothalamus induces renin release by activating peripheral adrenergic nerves (Zanchetti et al. 1976). Beta-receptors in the juxtaglomerular cells mediate these stimulatory effects, whereas alpha-receptors have opposite effects (Zanchetti et al. 1976). Renin release in response to upright posture, as indicated by plasma renin activity (PRA), is due to sympathetic activation and therefore can be considered a marker for adrenergic activity (Zanchetti et al. 1976). Previous studies have shown that

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