EUROPEAN JOURNAL OF PHARMACOLOGY 21 (I973) 53-60.

NORTH-HOLLAND PUBLISHING COMPANY

MESCALINE AND LSD: DIRECT AND INDIRECT EFFECTS ON

$EROTONIN-CONTAINING
H.J. HAIGLER

NEURONS IN BRAIN

and G.K. AGHAJANIAN

Departments of Psychiatm" and Pharmacology, Yale University School of Medicine,

and the Connecticut Mental Health Center. New Haven, Connecticut 06319, U.S.A.

Received 25 September 1972

Accepted 4 October 1972

H.J. IIA1GLER and G.K. AGHAJANIAN, Mescalbw and LSD: direct and indirect effects on serotonin-containbzg
neurons in brahe, European J. Pharmacol. 21 (1973) 53-60.
The effects of mescaline and d-lysergic acid diethylamide (LSD) applied by micxoiontophoresi$ to single raphe
neurons were compared to the effects of mescaline and LSD given systemically. LSD inhibited all raphe cells when
given intravenously (i.v.) or microiontophoreticatly. No decrease in action potential size was seen in either case
during the onset or recovery stages. Mescaline i.v., 2-8 mg/kg, produced an inhibition of a sub-population of these
ceils. As in the case of LSD, there was no decrease in action potential size. Microiontophoretic mescaline produced a
dowing of firing rate at high ejection currents. In contrast to i.v. or microiontophoretic LSD or i.v. mescaline, the
dowing produced by microiontophoretic'mescaline was always associated with a decrease in action poten:ial size.
Furthermore, there was no correlation between the populations of cells depressed by microiontophoretic mescaline
and i.v. mescaline. These data indicate that mescaline has differing effects on raphe neurons depending on whether it
is given systemically or microiontophoretically. In contrast, LSD given systemically or microiontophoretically has
similar effects on raphe neurons.
Microiontophoresis

Mescaline

d-Lysergic acid diethylamide

1. Introduction

5-HT)

Since the effects ofd-lysergic

acid diethylamide
(LSD) and mescaline (3,4,5-trimethoxyphenylethylamine) on autonomic
function and behavior are simiiar (Wolbach et al., 1962) these two drugs may share

Woolley
and Shaw,
1954).
By histofluorescence
methods it has been found that 5-HT is contained in
the neurons of the raphe nuclei of the brain stem
(DahlstriSm and Fuxe, 1965). These cells are consistently and uniformly inhibited by the systemic ad-

a common site of action. In various species, cross

ministration of LSD (Aghajanianet al., 1970a). Fur-

tolerance

thermore,

occurs

between

LSD and mescaline

(Bales-

trieri and Fontanari,

1959; Appel and Freedman,
1968). A peripheral mechanism does not seem to account for such cross tolerance since prior treatment

receptive

sites

the direct,

in the

CNS (Gaddum,

microiontophoretic

1953;

application

of LSD and serotonin upon raphe neurons results in

an inhibition
of firing similar to that seen with systemic administration
of LSD (Aghajanian
et al.,

with mescaline does not reduce brain levels of LSD

1972). Systemic administration of mescaline, 2-4

(Winter,
1971). Snyder and Richelson (1970) have
proposed that mescaline may assume a conformation
resembling a portion of the LSD molecule. Taken together,
these data suggest that LSD and mescaline
may act on the same receptor site in the CNS.
It has been postulated
that LSD has its central

mg/kg, was found to inhibit a sub-population

of
raphe neurons (Aghajanian et al., 1970b). Therefore,
the question arises as to whether the sub-population
of raphe neurons inhibited
by systemically
administered mescaline is also inhibited by microiontophoretically applied
mescaline.
Because of the structural

effect

similarity

by acting

on serotonin

(5-hydroxytryptamine;

1
L,,

between

norepinephrine

and m_scaline

end

54

H.J. Haigler,G.K. Aghajanian.Mescalineand LSD

the fact that catecholamine terminals have been observed in the area of the raphe (Fuxe, 1965) norepinephrine (NE) was also studied,

A total of 40 male albino rats (Charles River Laboratories. Inc., Wihnington, Mass.), 2-3 months of age,
weighing _30-_90 g were used for these studies. Animals were anesthetized with chloral hydrate, 400
m_kg, and mounted in a stereotaxic instrument. A
burr hole was drilled in the midline of the skull slightly anterior to the lamdoidal sutures, in preparation
for lowering electrodes into the midbrain, the dura
mater and pineal body were removed and the hole
waslinedwithbone wax.
Recordings were made from either one barrel of a

tartrate, 5 X 10-2 M (pH 3.5); and mescaline sulfate

0.5 M (pH 3.5). Since persistent leakage effects have
been found in iontophoretic
studies with LSD
(Bloom et al., 1964), a dilute solution of this drug
was used to avoid tile need for excessive holding currents. NaC1 was added to facilitate passage of ejection
current (Curtis and Crawford, i969).
Raphe units were tentatively identified by their
characteristic slow rate (approximately 0.5-2 spikes/
sec), their regular rhythm, and a location in or near
the midline ventral to the aqueduct. The latter was
indicated by a zone of relative electrical silence. The
unit activity was passed through a high input-impedance amplifier and displayed on an oscilloscope. Integrated unit rates were followed with an electronic
counter whose analog output was plotted on a potentiometric recorder. An oscillographwas used to record unit spikes directly. Units exhibiting a stable

fused 5-barrel micropipette or from a single barrel

electrode attached alongside a standard 5-barrel micropipette, forming a 6-barrel electrode. 5-barrel _lectrodes were constructed and filled throu_ capillary
action by the fiber glass method of Tasaki et al.
(1968) in a manner previously described (Aghajanian
et al., 1972). 6-barrel electrodes were constructed
using a technique sinrilar to those described by
Krnjevic and Schwartz (1967), Curtis (1968a), and
Oliver (1971), as follows. The 5-barrel micropipette
was broken back to a tip diameter of between 5 and
10_ and then a single, fiber glass filled, micropipette
was placed adjacent to the 5-barrel micropipette using
a micromanipulator. The 6th barrel was attached to
the 5-barrel pipette with dental acrylic which was
later coated with lucite dissolve in cis.l,2-dichloroethylene. The 6th barrel, which was of improved
quality for purposes of recording, protruded 5-10/a
beyond the other barrels. In vitro, the impedance of
the recording barrel was usually between 5 and
15 M_ measured at 1000 Hz. 2 barrels, those for recording, and current balance, were filled with a solution on 2 M NaCI saturated with fast green. The currents used to eject drugs from the drug barrels were
balanced by applying an overall current through the
balance barrel equal and opposite to the net current
flowing through the drug barrels (Salmoiraghi and
Weight, 1967). The drug barrels were filled with varying conabinations of the following drugs: LSD bitartrate 5 X 10-4 M in 0.05 M NaCI (pH 3.5); I-NE bi-

baseline rate and waveform for 5 min were used for

the i.v. or microiontophoretic
experiments. Drugs
were ejected from the micropipette barrels by turning
the direct current source from 10 nA 'backing' to
20-100 nA of ejecting current. In some casesmescaline, 2-16 mg/kg, was given over a 10-sec interval and
in small volumes, 0.1-0.2 ml, i.v. via a tail vein. In
such cases LSD was also usually given after a partial
or complete recovery from the effects of i.v. mescaline had taken place.
Locations of the electrode tips were marked by
passing a lO-20-/aA current for 10 min through the
balance channel which was filled with the fast green
solution (Thomas and Wilson, 1965). Animals were
perfused through the left ventricle with a solution of
5% glutaraldehyde solution in 0.9% saline. Serial frozen sections (50/.t in thickness) were cut, mounted,
and then stained with neutral red. The location of the
electrode tip was indicated by a green dye spot 2550/.t in diameter, usually surrounded by a vacuity. In
a separate group of animals, histochemical fluorescence studies were carried out by a modification of
the formaldehyde condensation technique of Falck et
al. (1962), as previously described (Aghajanian and
Asher, 1971), in order to confirm the location of cells
with 5-HT fluorescence (Dahlstr6m and Fuxe, 1965;
Bj6rklund et al., 1971). In 67 of a total of 77 cells
studied, the recording sites, as indicated by dye spots,
were found in portions of the dorsal and median
raphe nuclei of the midbrain. These nuclei correlated

2. Materials and methods

I,
i

}
i

H.J. Hoigler. G.K. Agha]onian.

Mescaline

and LSD

55

_ _" a& . :o

""

CA

_'_ _.

_T"_-':
ql
a-.,---

"'.-_..

-*- _ -tL-. .

* ....

-. _- 7 .-__.

_"

o , .t.._.
_"

: _--.:_-."
_._""_'"I'_-w -" ._'..'
." - """_._:_..

_"_-L

._-.._._t,:"

--'.._'
.:.. "'_.- ..
. . _-_._._-:_.,

".,

. _ .t,o:..,-_*_,_..._
....... ..

.--:/,_-:
.-" ".'.-==._....:".:-.:.'_.-.'..:_:,_."-',_._m..':,,.
,L.

_,
_):,'-.
,-:.-'"_:_./%,.:'_."V_-{_.,._.._,i-i_
7"
_.;_.a-._.
7:'i ": t,_., ' ;-_%_2,:_"

"_'_"'_-::'.',
"L_: '.,_."J:_._ :_

Fig. 1. Relationship
of recording sites to location of S-HT neurons in the dorsal raphe nucleus of the midbrain. (A) In this
micrograph
the fast green spot (arrow) is surrounded by a halo and is located at the end of the electrode
track (neutral red
counterstain).
The fast green was ejected from the recording electrode. The rectangle encloses the ventral portion of the dorsal
raphe nucleus. (B) Fluorescence
micrograph showing the high density of fluorescent
cells in a site corresponding
to the area
encompassed by the rectangle in (A). SCP, superior cerebellar peduncle; CA, cerebral aqueduct; CG, lateral central gray.

with a dense population of yeUow-fluorescent cells.

The illustration of the procedure used for correlating
recording sites _th histofluorescence
is given in
fig. 1. Of the 67 raphe ceils tested, 65 were in the
dorsal and 2 in the median raphe nucleus; most of the
verified S-HI cell bodies have been found in the
former (BjOrklund et al., L971}.
Dosa_s of drugs given i.v. are in terms of the
weights of the following salts: LSD bitartrate and
mescaline hydrochloride. These were given in 0.9cA

3. Results

saline

ited

solution,

When mescaline, 2-16 mg/kg, was administered

systemically via the tail vein. 12 of 24 raphe units
tested were inhibited; the remainder showed either no
change (9) or a slight increase (3) in average discharge
rate. The cells inhibited by mescaline were located in
the ventral portion of the dorsal raphe nucleus. These
data are in agreement with a previous study (Aghajanian et al., I970a) that also showed that cells inhibby

effective
those

i.v.

mescaline

in inhibiting
unaffected

inhibition

produced

are found

in this area.

LSD

all of the

raphe

including

or accelerated
by

mescaline

cells

by i.v. mescaline.
and

LSD

could

was

The
be

__:_
,_i,_

'_i:..... : _"_:_zA_'_i_i!_:_,_._u:___
_ _"_i_'i_:__!:_'_ _=_ _d_:'_" _ia,_
_'_i_i;_;'_
_ .... _ "__":_:_
_*'_=_"_'_T'__
._"-._/_i_.... '_

56

: ;_
:_'_":'
........_..............
:_

_i_i_=_';'_:
_ _!: ......t"....... -"_'_'i_i;
;'71
...._ _

;_!

H.J. Haigler, G.K. Agha/anian, Mescaline and LSD

differentiated
by the fact that during the inhibition
after i.v. mescaline, 1 or 2 discharges could be elicited
by noxious stimulation (e.g. firm pressure on the hind

line. In addition, the cells depressed by microiontophoretic

mescaline
had uo particular anatomical
grouping, whereas cells responsive to i.v. mescaline

paw, 'toe pinch'). Such stimulation

was ineffective
when a raphe cell was inhibited by LSD.

were found in the ventral portion

nucleus.

Microiontophoretic
mescaline was administered to
67 raphe cells. In 32 there was little or no response,
Rate was depressed in 31 and increased in 4 of the
responsive cells. In 3 of the latter 4 cells the accelera-

It was noted that in the cells depressed by microiontophoretic

mescaline there was a reduction
in the
amplitude
of the extra-cellular
action potentials
(spikes) of these cells in association with the decrease

tion of firing during the microiontophoretic

mescaline seemed to be related to a cell death. In only ! of
the 67 cells was there a reproducible increase in firing

in rate. Such changes in action potential size were

therefore
studied more closely. When mescaline was
given i.v. reductions in firing rate were accompanied

rate. Depression of firing occurred when ejection currents of 60-100

nA had been on for at least l min.
During such depression, cells showed no response to

by increases in action potential size as is illustrated in

the top trace of fig. 2. However, when mescaline was
administered
by microiontophoresis
a decrease in ac-

noxious stimulation,
in marked contrast to responses
seen during the depression produced by i.v. mesca-

tion potential
size accompanied
any slowing in the
firing rate of raphe cells. In the example shown in
fig. 2 (bottom
trace) this decrease in amplitude occurred after the ejection of mescaline at 100 nA for

st IV

several min. The spike

amplitude

IlllllllIIi[!
'"'"
I[llil!llll
o,f
IrI I''r
.......

II

I_

I[lllllll

I 3<
o

returned

quickly

, I

not
_ N<

size
ejection
was current
also seenhadduring
been

I ! It,
tSD
20

30 SEC

after 2.i.v.
Fig.
The
or amplitude
microiontophoretic
of extracellular
mescaline
raphe (M).
action
Thepotentials
slowing
seen after i.v. mescaline (top trace) is associated with an increase in action potential size. On the other hand, the slowing
seen after 2.5 min of direct mescaline ejection (bottom trace)
is accompanied by a decrease in action potential size. Notice
that the action potential size and discharge rate rapidly return to control after the cessation of mescaline ejection. In
other cases when the mescaline ejection current was continued, further decreases in action potential size occurred
leading to an apparent cell death. In this and all succeeding
figures, arrows indicate the point at which drugs were administered i.v. The period during which drugs were administered
by mictoiontophoresis is indicated by a horizontal line; the
number above the line refers to ejection current in nA.

,; :,i; :its,., ,_
.......
'! ltflil!iil'!_t'lll_
II .............
, Ii
._:,i _*._ ',,_:,,JJl

30 SEC
Fig. 3. The amplitude of extracellular raphe action potentials
after LSD given i.v. (top trace) and microiontophoretically
(bottom trace). In the top trace, as the cell slows, there _s a
slight increase in action potential size. The size of the action
potential returns toward baseline as the rate of discharge be-.
gins to recover. In the bottom trace 20 nA of LSD is administered microiontophoretically for 2.5 rain as indicated by the
horizontal line. As with i.v. LSD, there is an increase in the
action potential size in association with a decrease in rate.

i
i

to

LSDiv
#

100

tl['IlllrII

control A after
tion.
decrease
the mescaline
in spike

of the dorsal raphe

H.J. Haigler,G.K. Aghafanian,Mescalineand LSD

microiontophoretic

mescaline for one control cell.

The decrease in spike amplitude may indicate a local

anesthetic effect (Curtis, 1968b; Hoffer et al., 1971).
9 other control cells showed no clear cut responses to
mescaline or LSD when these drugs were administered either microiontophoretically
or i.v. When LSD

2401 LSoD
M
tl_.
lOO
_
ol
..........
NE M
M IV
4o loo
Vv/V

was given i.v., as discharge rate decreased, there was a

slight increase in the size of the action potential recorded from raphe neurons, as is illustrated in the top
trace of fig. 3. In contrast to mescaline, tile increase

_1201
_ oJ
_.
'_

in action potential size was also noticed when raphe

cell discharge rate decreased following the microiontophoretic application of LSD (fig. 3, lower trace),
To investigate the possibility that a local anesthetic-like effect of mescaline might be related in some
way to the inhibition produced by i.v. mescaline, the
drug was administered microiontophoretically
and i.v.
to the same cell in 17 cases (table 1). 9 cells were

121

reversibly inhibited
in action potential
crease in discharge
microiontophoretically
amplitude occurred

by i.v. mescaline with no decrease

size. 12 cells showed some derate when mescaline was applied
but marked decreases in spike
before total inhibition could be

achieved. It is significant that most raphe cells which

were hilly responsive to i.v. mescaline showed little
or no response to the microiontophoretic
application
of mescaline or vice versa (fig. 4, top and middle
traces; table 1). In only 4 of the 12 cases in which
microiontophoretic
application produced a depression in rate, was i.v. mescaline also effective (fig. 4,
bottom trace),
NE was applied by microiontophoresis
to 66 raphe
cells: 29 (44%) showed an increase in discharge rate;
15 (23%) showed a complete inhibition of discharge
Table 1
The effects of mescaline given microiontophoreticallycompared with the effects of i.v. mescaline on the rate of discharge of raphe cells,
Raphecell response

Number of raphe
cells studied

Microiontophoretic

l.v.

Depression
Depression
Depression

Nochange 7
Excitation
Depression 41
Depression 5

No change

57

M
60

M IV
_
" ' _ " t ......

MIV

od

lo MIN
Fig. 4. Effects of microiontophoretic
and i.v. mescaline(.M)
on the average discharge rate of single raphe neurons. Top
trace: notice that microiontophoretic
mescaline produces little, if any, depression in the discharge rate. llowever, both
microiontophoretic LSD and i.v. mescaline, 6 mg/kg, produced a marked inhibition in the discharge rate of the cell.
The occasional bursts of firing during recovery from the inhibition produced by i.v. mescaline are evoked by firm pressure upon the hind paw ('toe pinch')..Middle trace: the discharge rate of this cell was depressed by microiontophoretic
mescaline applied for 2.4 min. The ejection current was
turned off because there was a decrease in the amplitude of
the action potential which had been a sign of incipient cell
death in numerous other cells, l.v. mescaline, 16 mg/kg, did
not influence the average firing rate of the cell. Bottom trace:
microiontophoretic mescaline for 4 min produced a decrease
in firing. The ejection current was turned off at this point
due to a decrease in action potential size. l.v. mescaline, 4
mg/kg, produced a prolonged inhibition during which a toe
pinch would cause the cell to discharge once or twice. No
decrease in spike size was seen after the i.v. mescaline (cf.
fig. 2).

rate; and in 22 (33%) the discharge rate was unaffected. To investigate whether or not the response to
microiontophoretically
applied mescaline was related
to responses to NE, mescaline was applied microiontophoretically
or i.v. and NE microiontophoreticaUy to 46 raphe cells (table 2). There did not seem
to be a correlation between the responses to microiontophoretic mescaline and NE as had been reported
for cortical cells (Bradshaw et al., 1971), nor was
there any correlation between
mescaline and microiontophoretic

the response to i.v.

NE.

.........

58

_, ....................
r,r_'_'"_I

!-1..I.H_zigler,G.K. Agha/anian,MescalinetrtdLSD

Table2
Lack of correladon between the effects on raphe ceils of
mescaline given mictoiontophotetically or i.v. and the el'fects of norepincphrine administered microiontophoretically,

application ofmescaseem well correlated

by i.v. administered
some raphe cells are

O,licroiontophor-

(Microiontophor-.

unaffected by microiontophoretic application of mescaline but are completely inhibited by the systemic
administration of mescaline. The failure to obtain a

eric)

eric)

response to mescaline, even under extreme conditions

Depression
Excitation
Depression
Depression
No change
n.y.)
Depression
Excitation
Depression

Depression
Excitation
Excitation
No chan_
Excitation

5
4*
10
7
7

Depression
Excitation
Excitation

Depression

No change

No change
No change

Excitation

2
1
3
2
3

No change

Mescaline

Norepinephrine

Number of raphe
cellsstudied

ited by the microiontophoretic

line, this inhibition does not
with the inhibition produced
mescaline. On the other hand,

* In 3 of these cells the increase in rate during the microiontophoreticadministrationof mescalinewas associated with
a cell death.

(e.g., 100 nA for 5 min) from cells which were very

sensitive to systemic mescaline (e.g., 2 mg/kg) does
not support the view that the action of systemic mes.
caline on these raphe neurons is a direct one. In con.
trast, certain cortical neurons are highly responsive to
the direct application of mescaline with no reported
local anesthetic effect (Bradshaw et al., 1971). Nei.
ther did we find a correlation between response to
mescaline and NE administered microiontophoretically as has been reported for cortical cells (Bradshaw et
;tl., 1971). Moreover, there did not seem to be a relationship between responses to i.v. mescaline and responses to NE.
There was no indication of a local anesthetic effect

The similarity between the effects of mescaline

and LSD on autonomic function and behavior (Wolbach et al., 1962), the occurrence of cross tolerance
between the two drugs (Balestrieri and Fontanari,
1959; Appel and Freedman, 1968), and the possibility that mescaline mi_t approximate the structural
configuration of LSD (Snyder and Richelson, 1970),
all suggest that LSD and mescaline may have the same
site of action in the CNS. When LSD is administered
systemically to rats in doses comparable to those
which produce behavioral effects, the firing of serotonergic neurons in the raphe nuclei of the brain stem
is reversibly inhibited (Ao,.daajanian et al., 1970a).
When LSD is administered microiontophoretically
a
similar inhibition is obtained (Aghajanian et al.,
1972). These data, coupled with the fact that after
the systemic administration of mescaline a sub-population of raphe neurons is inhibited (Aghajanian et al.,
197Ob), indicate that there may exist a subpopulation
of raphe neurons which would be inhibited by the
microiontophoretic
application of mescaline. How-

in the group of cells inhibited by i.v. mescaline since

there was no decrease in action potential size. Moreover, these cells could still be made _o discharge by
toe pinch, and, less often, NE. With the intense currents used microiontophoreticaUy to eject the rather
concentrated solution of mescaline, there did seem to
be a local anesthetic effect on some cells, as indicated
by a slowing accompanied by a decrease in the amplitude of the action potential (Curtis, 1968b; Hoffer et
at., 1971). The extreme conditions were used to rule
out the possibility that the lack of a response to microiontophoretic mesca/ine was due to an inadequate
amount of the drug reaching the cell. The occurrence
of a local anesthetic effect would suggest that a sufficient amount of drug was, in fact, reaching the cell.
Under certain conditions cationic ejection current
alone can depress neuronal activity (Curtis, 1964).
However, the electrotonic effects of the ejection current were minimized by use of a balance channel (Sal.
moiraghi and Weight, 1967). Moreover, no effects
were obtained with high ejection currents of Na, indicating that the slowing seen with microiontophoretie mescaline is probably not due to a non-specific
current effect. These data indicate that mescaline is
being ejected in amounts sufficient to produce a local

ever, although some raphe neurons are partialbi inhib-

effect. However, this local effect does not resemble

4. Discussion

_,

H.J. Haigler. G.K. Agha]anian. Mescaline and LSD

59

the effects produced

by i.v. mescaline. This contrasts
with the similarity between the effects of LSD given
either systemically
or by microiontophoresis.
On a
biochenfical
level, LSD and mescaline also differ in
that LSD but not mescaline has been shown to de-

sory Committee for providing the LSD used in these studies.

Supported in part by NI.Mll Grants (MI1-17871 and MH14459) and the State of Cormecticut.

press the metabolism

of brain serotonin (Freedman
et
al., 1970).
A possible explanation
for the lack of correlation

References

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or
microiontophoretically
is that when mescaline is administered
systenlically,
an active metabolite
is
formed in the periphery.
Therefore,
when mescaline
is applied very close to the cell it would be relatively

Aghajanian,
and I.M.
Asher. Selective
1971, tlistochemical
rescence G.K.
of raphe
neurons:
enhancement |luoby
tryptophan, Science 172, 1159.
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G.K., M.It.
Sheard and
W.E. Foote.
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and mescaline:
comparison
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on single
unitsLSD
in

ineffective since there would be no opportunity

for it
tO be metabolized.
Two metabolites
of mescaline
have been studied
in man, N-acetylmescaline
and
3,4,5-trimethoxyphenylacetic
acid, but they did not

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physiological

and

psychological

effects

(Charlatnpous
et al., 1966). The primary metabolite
of mescaline
in rats, 3,4,5-trimethoxyphenylacetic
acid, has not been tested for its efficacy in rats
(Musacchio
and Goldstein,
1967). The possibility that
mescaline must be converted to this metabolite in rats
before it is effective on raphe cells has not
oul. In our experiments,
tile onset of the
of firing in the raphe cells is within 30-40
the i.v. injection of mescaline, suggesting
active metabolite
is formed this must occur

been ruled.
inhibition
sec after
that if an
extremely

rapidly to be responsible for the inhibition,

In conclusion,
it would appear that systemically
administered
mescaline acts upon raphe cells primarily indirectly
since the only direct mescaline effect
obtainable
was of a local anesthetic
type. Furthermore, it appears that responses to mescaline by either
route are unrelated
to responses to NE. Since both
LSD and mescaline can inhibit cells in the raphe nuclei when given systemically,
but only LSD readily
produces an inhibition
in these cells when applied

microiontophoretically,

one is

led to the conclusion

that these two drugs differ in their mode of action

upon raphe cells. The possibility
remains that LSD
and mescaline share a common site of action in some
other area of the CNS.

Acknowledgements
We thank the FDA-PHS Psychotomimetics

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