1955_evarts_4051_2.pdf

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LSD No. 166 (_102a)
C9rrected
version
M 500 effect on lateralge-
nlc atenucle
E.V., MARSHALL, W.H. (Bethesda, Maryland)
effects of lysergic acid die_hyl_m4de on the excitability
_e
j
of the lateral _eniculate.
....
Transact.Am.Neurol.Assoc. 58 (1955)
80,
Lysergic acid diethylamide (LSD) has been shown
to reduce the
tmpli-
tradeof the
postsynaptic potential
recorded
in the
lateral geniculate
nucleus
following
near
maximal
shocks applied
to
the
optic
nerve
of the
nembutalized
cat.
While geniculate transmission
is markedly affected
by LSD in
doses
of
0.03
mg/kg,
the
cortical response evoked
by
stimulation
of genicuhte radia-
tion fibers
is highly
resistant to LSD.
Intracarotid administration
d
LSD
;n
doses
as high
as
1.5 mg/kg
did
not
depress
this cortical
response.
In
the
prepc.ration described above,
a tetanus of
near maximal
shocks
applied to
the
optic
nerve at
300/see
causes marked recruitment
of
the
LSD-depressed
9ostsynaptic geniculate potentials.
The
effects
of LSD
which were
observed
i_
nembutalized animals were also observed in animals
decerebrated by
a
n'fidcollicu_r brain stem sect/on. The
similarity of
e_ects
of LSD
in nembu-
t_d/zed and dc_erebrate preparations indic,xtes
that
the effect_
o_ LSD
are
_ot a
function of
nembutal anesthesia.
The
progressive
recr,uitmem
p_duced
_),"_ tetanus in a preparation under
the
effects of LSD is similar to the
_it:_ent
which
has be,m
shown
to
occur
during
the
state of subno_ty
a
•
cb_;_h
feqtowsoptic
nerve
stimulatios. The
similarity
be__wee_ effects of
the
]_SD
s_d
the ef]r_ts of a condi6oning tet_,us suggested that a n'_o;ethor--
_y_
of the effects of LSD on
the genic_.qateexdVabiii_y
t_emade_
_"_order to ,__-,cw mca'c,accurate temper/son _..twee_ genicuhte subnor-
a
_ity _nd the
effects
of LSD.
Mace_foL_ and Mt_hoda._Cat_
weighing betw_,_a 2.0 and 4.0 kg we._,=anesthetized
wi_
ggliuna
_'mtobarb_tal, 30 _._g/_g. The fight _ic herr(
w_tn
exp_s_..C The )eft
cere-
L_,r'_ecc_ea_wa_
exposed under c_tinnously flowhag Tyrode's _iution warmed to 370C.
P,
recc,
rd of
eortieat _._tJvity _'a_ obt_ineg with
a
pore
electrode
pl_.c_:don fi;e laterz!
_rr_. Gemcui_te res'0on._e_to optic nerv_: _t_mulati_ were
recorded
from
g
_teet needle,
izt_date4 to _hc tip, with a t_p
diameter
of __._rox_mzte_y 10Og.
TD.s
ele_.,rode was. ¢tae_
the
_erat genieuiate n,icie_s by
z
stereot_xic
in_ruuner.,t.
The ,;_os_t;.o_of tl'_ ele¢-
_
w_
marked electroly_ical!y
_d c_e-ck_:_h_stoiog_c_d_y.Tc_t _)_irs
ofnear
maximal
_ho'_k_were
a_,lied
to _he <_dc _._rve,
c,w=_dmu_a_i_g ele<t:_a¢.
_°e_i_g r_ the
expos_
nerv_ t_vt
otk_r
attached to _:i',::,
sc!er_ 7he i._'.terv_.lbetween
t_.. _h_.k_
o_
_the
test Ixair
v_,,ri_
between 2.5 and
V.)0.9ras_,
e_c_ intev_l being approzGn_t..a_)' 25%
greater
_
the preceding interval. L', steadies c.n the e_zdtzb[l_ty ,.':yel_d_rrin_ _t;r, nrrnziity_ a
ma_:ctetam_ of
near
maximal
sh_wJ,:_
_t4_i_l'_e_preceded
the test _z. I)iffere_t degrees
of
_abc_rmaliL_ were produee_ by
garvi_g
the interval betweer_ tb_
.n_
of the ccmdi-
tio_ng tetanus and the first
n}_ck 04
the test pa_r.
T'r_e
interv_._ _tween the test
pair
and conditioning tetanus were 50, 100, 170,
290
and 470 rnnee. _n studies of the effect_
o_ LSD
on
the genieuiate e_citability cycle, LSD was administered intravenously in
qumatities of
0.16 mg/kg. Photographic records of oscillographic traee_ of
geniculate
_TS,
(
responses
were obtained,and
the
amplitudesof the postsyzmpti¢
geniculate
po¢entials _
resulting from the test
pair
of comparlso_swere made between the effects were
plotted
on
semilogarlthmicpaper,and
shocks
were measured.Excitability cycles of LSD
and
the effects of the conditioningtetanus.
]_.SULTS
A.
The effects of LSD
on
the
geniculate excitability
cycle.mLSD
in
doses of 0.16
mg/kg
intravenously caused
a 60 to
90% decrease in
the amplitude
of the
postsynaptic response
to
the
first shock
of
the test
pair. The amplitude of
the postsynaptic potential
resulting
from the
second
shock of the
pair
varied
with
the
pair
separation. Recruitment
occurred at
pair separations of from
2.5 to 16
msec.
In
some
preparations
the
amplitude
of the
_cond
soma
spike was
3
or 4
times greater than that of the first.
Maximal recruitment occurred at
pair separations
of
from
8 to 13 msec. At
pair
separations
greater
than
16 msec,
the
amplitude
of
the second post-
synaptic potential
became less
than that
of the.
first,
reaching
a
minimum
at
25 to 32
msec
pair separation,
at
which
point
it was
approximately
one imlf
the amplitude of the first
postsymptic
potential.
This
subnommlity induced
by the first shock of the
pair
extended
to approximately
I second.
B.
The
effects
o[ conditioning tetanus on the excitability cycle.oThe
curves of recruitment
and
subnormality obtained by
plotting
the am-
plitudes of the
paired shocks
varied, depending on the degree of subnor-
mality
in which
the paired shocks
were presented. When
the
interval be-
tween
the
conditioning
volley and
the
first
shock
of
the test pair
was less
than
30 msec, little
if any
recruitment
occurred.
When the interval between
the
conditioning
tetanus
and the
test pair wa.¢
170 msec,
the
excitability
cycle closely resembled the
excitability
cycle obtained in preparatiorm
that
had received 0.08 to 0.16
mg/kg LSD.
At
this
interval
( 170 msec),
recruit-
ment occurred at
pair
separations between
2.5
and 16
reset, with ma:dmum
recruitment at 8 to 13 msec
pair separations.
Following
the
petqod of recrt_it-
ment,
a period of
maximum
25
to 32 reset.
subnormality
c_curred
at
pair sepa_tions
of
Di,rc**ssion._The
response of
the
geniculate
to a
te,anic
stimulus in a
preparation treated with
LSD is
similar
to the
genieuiate response
to
a
tetanic stimulus
presemed
during
subnormality
following a
conditioning
tetanus.
This s_milarity between
the eff_ts of LSD
and of sub_o,wnati
D"
extends
to
the gcnicul_te excitability cycies whkh have _
ob_dned
in
these experiments.
The
explanation
,:>fthem,',vves
o_ recruitment and
sub-
normality
for
vaired
shocks
in the two condi_k,n_ is n<a clear at the present
time, (.>tie may speculate, however, _hat, ,,[_c_ain
respects, LSD
produces
the _me
alter;ttion
of the chemica! ,:>_
meta_,_tic s_te of g,'micutate syr_pses
as is produc_ by the transmission
of
tl_aei..'x_p_,isem
genera*ed by optic l_e_ve
sdm_dafi<m.
w4 (E
9u_3)
NKT/ev
756
:':i'_:

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