Secondary metabolites from three Florida sponges with antidepressant activity.
ABSTRACT Brominated indole alkaloids are a common class of metabolites reported from sponges of the order Verongida. Herein we report the isolation, structure determination, and activity of metabolites from three Florida sponges, namely, Verongula rigida (order Verongida, family Aplysinidae), Smenospongia aurea, and S. cerebriformis (order Dictyoceratida, family Thorectidae). All three species were investigated chemically, revealing similarities in secondary metabolites. Brominated compounds, as well as sesquiterpene quinones and hydroquinones, were identified from both V. rigida and S. aurea despite their apparent taxonomic differences at the ordinal level. Similar metabolites found in these distinct sponge species of two different genera provide evidence for a microbial origin of the metabolites. Isolated compounds were evaluated in the Porsolt forced swim test (FST) and the chick anxiety-depression continuum model. Among the isolated compounds, 5,6-dibromo- N,N-dimethyltryptamine ( 1) exhibited significant antidepressant-like action in the rodent FST model, while 5-bromo- N,N-dimethyltryptamine ( 2) caused significant reduction of locomotor activity indicative of a potential sedative action. The current study provides ample evidence that marine natural products with the diversity of brominated marine alkaloids will provide potential leads for antidepressant and anxiolytic drugs.
- SourceAvailable from: Olivier P Thomas[show abstract] [hide abstract]
ABSTRACT: Nine bromotyrosine-derived compounds were isolated from the Caribbean marine sponge Verongula rigida. Two of them, aeroplysinin-1 (1) and dihydroxyaerothionin (2), are known compounds for this species, and the other seven are unknown compounds for this species, namely: 3,5-dibromo-N,N,N-trimethyltyraminium (3), 3,5-dibromo-N,N,N, O-tetramethyltyraminium (4), purealidin R (5), 19-deoxyfistularin 3 (6), purealidin B (7), 11-hydroxyaerothionin (8) and fistularin-3 (9). Structural determination of the isolated compounds was performed using one- and two-dimensional NMR, MS and other spectroscopy data. All isolated compounds were screened for their in vitro activity against three parasitic protozoa: Leishmania panamensis, Plasmodium falciparum and Trypanosoma cruzi. Compounds 7 and 8 showed selective antiparasitic activity at 10 and 5 μM against Leishmania and Plasmodium parasites, respectively. Cytotoxicity of these compounds on a human promonocytic cell line was also assessed.Marine Drugs 01/2011; 9(10):1902-13. · 3.98 Impact Factor
Article: Nature against depression.[show abstract] [hide abstract]
ABSTRACT: Depression is a major health problem currently recognized as a leading cause of morbidity worldwide. In the United States alone, depression affects approximately 20% of the population. With current medications suffering from major shortcomings that include slow onset of action, poor efficacy, and unwanted side effects, the search for new and improved antidepressants is ever increasing. In an effort to evade side effects, people have been resorting to popular traditional herbal medicines to relieve the symptoms of depression, and there is a need for more empirical knowledge about their use and effectiveness. This review provides an overview of the current knowledge state regarding a variety of natural plant products commonly used in depression. Herbal medicines discussed that have been used in clinical trials for the treatment of mild to moderate depression states include the popular St. John's wort, saffron, Rhodiola, lavender, Echium, and the Chinese formula banxia houpu. In addition, new emerging herbal products that have been studied in different animal models are discussed including Polygala tenuifolia, the traditional Chinese herbal SYJN formula, gan mai da zao, and Cannabis sativa constituents. A comprehensive review of the chemical, pharmacological, and clinical aspects of each of the reviewed products is provided. Finally, recent preclinical studies reporting the antidepressant action of marine-derived natural products are discussed at the end of the review.Current Medicinal Chemistry 03/2012; 19(14):2229-41. · 4.07 Impact Factor
Article: Quinone/hydroquinone sesquiterpenes[show abstract] [hide abstract]
ABSTRACT: The quinone/hydroquinone sesquiterpenes of drimane or rearranged drimane skeletons constitute a wide and diverse group of secondary metabolites of mixed biogenesis. These compounds are mainly of marine origin and their interest is not only for the variety of isolated structure but for the interesting biological activities that they present. In this paper a series of quinone/hydroquinone sesquiterpenes of natural origin that have been reported to date is presented. The structures of these compounds are gathered into eight groups with reference to their biological activities and compounds synthesised. Keywords: Sesquiterpenes quinone/hydroquinone, drimane, rearranged drimane. Sesquiterpene quinones/hydroquinones having a normal dri-mane skeleton or a rearranged drimane skeleton, represent a promi-nent class of mixed biogenesis metabolites that incorporate a bi-cyclic sesquiterpene unit coupled to a quinone or quinol . Those compounds have attracted the attention of researchers both through the abundance of structural variants and the wide range of remark-able biological properties ascribed to specific samples . Although most sesquiterpene quinones/hydroquinones have been isolated from sponges, some of them have been reported from brown algae  and at least three compounds were described from a fungus [4-6]. We present herein a compilation of the naturally occurring ses-quiterpene quinones/hydroquinones, whose terpenoid unit is bi-cyclic, that have been isolated to date. The following collection comprises a listing of structures, along with tables that include the source of isolation, biological activities and the literature source. Some compounds have also been synthesised and these are marked with an asterisk.Mini-Reviews in Organic Chemistry 01/2010; 7:230-254. · 1.06 Impact Factor
Secondary Metabolites from Three Florida Sponges with Antidepressant Activity
Anna J. Kochanowska,†Karumanchi V. Rao,†Suzanne Childress,‡Abir El-Alfy,‡Rae R. Matsumoto,‡Michelle Kelly,§
Gina S. Stewart,⊥Kenneth J. Sufka,‡,⊥and Mark T. Hamann*,†,‡
Departments of Pharmacognosy, Pharmacology, and Psychology and the National Center for Natural Products Research, School of Pharmacy,
The UniVersity of Mississippi, UniVersity, Mississippi 38677, and the National Center for Aquatic BiodiVersity and Biosecurity, National
Institute of Water and Atmospheric Research, Auckland, New Zealand
ReceiVed July 26, 2007
Brominated indole alkaloids are a common class of metabolites reported from sponges of the order Verongida. Herein
we report the isolation, structure determination, and activity of metabolites from three Florida sponges, namely, Verongula
rigida (order Verongida, family Aplysinidae), Smenospongia aurea, and S. cerebriformis (order Dictyoceratida, family
Thorectidae). All three species were investigated chemically, revealing similarities in secondary metabolites. Brominated
compounds, as well as sesquiterpene quinones and hydroquinones, were identified from both V. rigida and S. aurea
despite their apparent taxonomic differences at the ordinal level. Similar metabolites found in these distinct sponge
species of two different genera provide evidence for a microbial origin of the metabolites. Isolated compounds were
evaluated in the Porsolt forced swim test (FST) and the chick anxiety-depression continuum model. Among the isolated
compounds, 5,6-dibromo-N,N-dimethyltryptamine (1) exhibited significant antidepressant-like action in the rodent FST
model, while 5-bromo-N,N-dimethyltryptamine (2) caused significant reduction of locomotor activity indicative of a
potential sedative action. The current study provides ample evidence that marine natural products with the diversity of
brominated marine alkaloids will provide potential leads for antidepressant and anxiolytic drugs.
Marine sponges have been a prolific resource of a huge diversity
of secondary metabolites over the past 50 years of discovery.
Sponges in the order Verongida have been reported to show unusual
biochemical profiles characterized by the absence of terpenes and
the production of sterols and brominated compounds biogenetically
related to tyrosine.1
Many reported indole and pyrrole-imidazole alkaloids play a
defensive role and exhibit interesting types of bioactivity, including
calmodulin antagonism, cytotoxicity, antimicrobial, antiviral, an-
tiparasitic, anti-inflammatory, and Ca2+-releasing activity.2,7,10,12,14
Bromination of members of this class of alkaloids occurs frequently
when isolated from the marine environment and is catalyzed by
haloperoxidases that oxidize halogen anions from seawater.3The
utility of these metabolites in neuropsychiatric disorders remains
to be characterized.
Central nervous system (CNS) disorders are common worldwide,
with about one-fourth of adult Americans suffering each year from
a diagnosable psychotic disorder.4Since the 1960s depression has
been linked with decreased functional amine-dependent synaptic
All clinically used antidepressant drugs suffer from serious side
effects, which may include metabolic, cardiovascular, and sleep
disorders or increased suicidal thoughts and aberrant behavior.
These drugs also require approximately 6 weeks before their full
therapeutic effect occurs. Most known antidepressant drugs act as
either monoamine oxidase inhibitors or reuptake inhibitors of
noradrenaline and/or serotonin. These groups of drugs increase the
concentration of monoamines in brain, facilitating their binding to
receptors.5In addition, serotonergic neurotransmission systems have
been implicated in the neuronal regulation of mood; thus enhance-
ment of serotonin transmission is a recognized basis for the
treatment of different types of depression.
To date, 14 types of serotonin receptors, grouped in seven
families, have been reported to be expressed in mammalian CNS.6
Research leading to selective serotonin receptor ligands is extremely
important to further understand the role and function of these
receptors. Considering the structural similarity of indole alkaloids
and the endogenous monoamine serotonin, many efforts have been
directed toward isolation and synthesis of serotonin-like molecules,
which could possibly possess affinity to different 5HT receptors.
Brominated marine indole alkaloids have been previously reported
by Hu et al. to possess high affinity for human serotonin receptors.7
In order to further define the structure–activity relationship and
search for possible leads to control depression, we have carefully
examined the ethanol extract of three sponges collected from the
Florida Keys. The sponges were collected from a variety of locations
in the Florida Keys and separated based on morphology and color.
The samples were identified as three species, two of which are well-
known: V. rigida (Esper, 1794) (order Verongida, family Apl-
ysinidae) and S. aurea (Hyatt, 1875) (order Dictyoceratida, family
Thorectidae), and a third, S. cerebriformis (Duchassaing & Mich-
elotti, 1864), is less common and separated based on subtle
differences of morphology and coloration from the other two
species. A table describing key field and histological characteristics
that differentiate between the three species is available in the
Supporting Information. Several known compounds were isolated,
and those that bear structural similarity to serotonin were evaluated
in two established animal models predictive of antidepressant drug
action, namely, the rodent FST and the chick anxiety-depression
* To whom correspondence should be addressed. Tel: 662-915-5730.
Fax: 662-915-6975. E-mail: email@example.com.
†Department of Pharmacognosy.
‡Department of Pharmacology.
§National Center for Aquatic Biodiversity and Biosecurity, National
Institute of Water and Atmospheric Research.
⊥Department of Psychology.
J. Nat. Prod. 2008, 71, 186–189
10.1021/np070371u CCC: $40.75
2008 American Chemical Society and American Society of Pharmacognosy
Published on Web 01/25/2008
Results and Discussion
Exhaustive extraction of 3 kg of V. rigida yielded 211 g of crude
extract. The fractionation and further purification (described in detail
in the Experimental Section) of the crude extract yielded the
following known metabolites: 5,6-dibromo-N,N-dimethyltryptamine
(1),85-bromo-N,N-dimethyltryptamine (2),8aplysinopsin (3),9,10
makaluvamine O (9),7arborescidine C (5),116-bromoaplysinopsin
(6),12,135,6-dibromoabrine (7),14and small amounts of aureol (8)8
and ilimaquinone (4).15,16
The ethanol extract of S. aurea was purified as described in the
Experimental Section to yield aureol (8)8and four indole alkaloids,
which were identified as 5,6-dibromo-N-N-dimethyltryptamine (1),8
2′-des-N-methylaplysinopsin (10),176-bromoaplysinopsin (6),12,13
and makaluvamine O (9).7
S. cerebriformis (6 kg) yielded 260 g of extract, which exhibited
significant activity against Candida albicans and MRS (IC50of 15
µg/mL for both pathogens). The crude extract of this sponge was
found to contain primarily ilimaquinone (4),15,16but polar fractions
examined by HRMS showed also the characteristic peak of 5,6-
Among the compounds isolated, 6-bromoaplysinopsin (6) was
previously reported to exhibit significant activity against Plasmo-
dium falciparum and to display high affinity for human serotonin
5HT2receptor subtypes.7Makaluvamine O (9), 5,6-dibromo-N,N-
dimethyltryptamine (1), and aureol (8) were reported to display
significant activity against the HCT-116 colon carcinoma cell line.14
Both dimethyl bromotryptamine derivatives were reported as
antimicrobial agents, and according to Tymiak and Rinehart,
dibromotryptamine (1) had significantly greater antimicrobial
activity than the monobrominated analogue (2).12Aplysinopsin (3)
was previously isolated from different sponge species9,10,12and
was found to possess antineoplastic activity.10
All the compounds previously reported from other Verongida
species were identified by comparison of their spectral data with
literature values. Similar patterns of secondary metabolite produc-
tion were found in species belonging to two distinct orders
(Verongida and Dictyoceratida), providing evidence for a common
microbial source of these compounds. Recent isolation of both
brominated tryptamine derivatives from algae Bryopsis sp. in our
laboratory strengthens this hypothesis.
Due to limited amounts of isolated compounds, only four of them
could be tested in the Porsolt forced swim test and chick
anxiety-depression continuum models. The locomotor activity test
was performed to demonstrate that reductions in immobility time
showed by the isolated compounds were not a secondary conse-
quence of their nonspecific stimulant actions.
5,6-Dibromo-N,N-dimethyltryptamine (1) was evaluated in the
forced swim test and chick anxiety-depression model. The forced
swim test showed that 1 possesses significant antidepressant-like
activity (F[4.44] ) 31.56, p < 0.01) (Figure 1). Post hoc
comparisons of individual doses to the vehicle control showed that
1 significantly reduced the immobility time only at the 20 mg/kg
dose (q ) 8.28, p < 0.01).18
In the chick anxiety-depression continuum model,19socially
raised chicks are separated from conspecifics during a 2 h test
session. Vehicle-treated chicks displayed high rates of vocalizations
during the initial 5 min time block that declined over the next 20–25
min period to approximately 50% of the initial rate and remain
stable throughout the remainder of the test session. Previous
studies19have shown the first 5 min block to model the anxiety
phase, whereby a diverse set of anxiolytic compounds reduce
distress vocalizations, and that the last 90 min of the test session
models the depressive phase of the model, whereby antidepressants
increase distress vocalizations (i.e., block the onset of behavioral
despair). In the present study, the 30 mg/kg dose of 1 possessed
both anxiolytic and antidepressant properties by attenuating separa-
tion distress vocalizations in the anxiety phase and elevating
separation distress vocalizations in the final 30 min of the depression
phase of the model, respectively (Figure 2).
According to findings of Dukat et al., the two-atom chain that
separates the indole from the terminal amine group is crucial to
the binding of tryptamines to the 5HT1Ereceptor, and any branching
has been reported to reduce the affinity.20Research conducted by
Glennon et al. revealed that replacing the primary amine moiety
with a secondary or tertiary amine increases the lipophilicity of
the molecule and makes it less prone to metabolism, hence
improving drug-like properties.21
Interestingly, compound 2, differing from 1 only by one bromine
atom, did not exhibit antidepressant-like activity, but instead showed
a significant sedative effect (t ) 3.55; p < 0.05) (Figure 3b).
Aplysinopsin (3) and ilimaquinone (4) did not show any significant
antidepressant-like activity in the rodent swim test.
Figure 1. Reduction of immobility time in the forced swim test by
Figure 2. Effects of 5,6-dibromo-N,N-dimethyltryptamine (1) on
separation distress vocalization rates during the anxiety phase (0
to 5 min, panel A) and the depression phase (30 to 120 min, panel
B) of the test session. * indicates a significant decrease (i.e.,
anxiolytic effect) and ** indicates a significant increase (i.e.,
antidepressant effect) of vocalization rate compared to vehicle-
treated chicks. All ps< 0.05.
Metabolites from Sponges with Antidepressant ActiVityJournal of Natural Products, 2008, Vol. 71, No. 2 187
In order to confirm that reduction of immobility in FST induced
by the tested compounds is true and not a result of a nonspecific
stimulant action, the effect on locomotor activity was determined,
whereby a nonspecific stimulant action is reflected as a hyperlo-
comotive effect. Analysis of variance revealed an overall significant
difference between the treatment groups (F[6; 38] ) 3.10, p <
0.05). However, Bonferroni’s multiple comparisons post hoc test
revealed that there were no statistical differences between any of
the tested compounds and their respective vehicle controls. Such
results demonstrate that the observed antidepressant-like effect of
5,6-dibromo-N,N-dimethyltryptamine (1) is not associated with a
stimulant action. In fact, 1 caused a nonsignificant trend toward
decreasing locomotor activity, which would not account for its
significant reduction of immobility time in the FST.
General Experimental Procedures. The1H and13C NMR spectra
were recorded in CDCl3, MeOD, and DMSO-d6 on an NMR spec-
trometer operating at 400 MHz for1H and 100 MHz for13C NMR.
The MS spectra were measured using a Bioapex FTESI-MS with
electrospray ionization and on a Bruker microTOF instrument. TLC
was carried out on precoated silica gel G254or aluminum oxide ALOX-
100 UV254(500 µm) plates. HPLC was carried out on a Waters system
with a Waters 2487 detector.
Animal Material. S. aurea was collected from the Florida Keys in
August 2005. The sponges were collected from shallow coral reef
habitat between 6 and 24 m depth at Key Largo, Florida, in July and
August 2005. Voucher specimens have been deposited in the Natural
History Museum, London (BMNH 2007.4.23.1 [University of Missis-
sippi voucher 05FL-020(3)]; BMNH 2007.4.23.2 [University of Mis-
sissippi voucher 05FL-027]).
V. rigida was collected from shallow coral reef habitat between 3
and 21 m depth at Key Largo, Florida, in July and August 2005.
Voucher specimens have been deposited in the Natural History
Museum, London (BMNH 2007.4.23.3 [University of Mississippi
voucher 05FL-020(2)]; BMNH 2007.4.23.4 [University of Mississippi
S. cerebriformis was collected from shallow coral reef habitat
between 3 and 21 m depth at Key Largo, Florida, on July 1 and August
7, 2005. Voucher specimens have been deposited in the Natural History
Museum, London (BMNH 2007.4.23.5 [University of Mississippi
voucher 05FL-020(1)]; BMNH 2007.4.23.6 [University of Mississippi
Extraction and Isolation. The sponge S. aurea was stored frozen
until extracted. A sample of the sponge collected from Jamaica in
November 2002 (35 g) was lyophilized, crushed, homogenized, and
then extracted with ethanol at room temperature, yielding 1 g of extract.
A second sample of sponge extract was obtained after grinding and
exhaustive extraction with ethanol and yielded 21 g. TLC analysis
indicated that the extracts contained various minor alkaloids. The
extracts were subjected to silica gel vacuum liquid chromatography
and eluted in order, with hexane (100%), hexane-acetone (9:1, 3:1,
1:1), acetone (100%), chloroform-methanol (1:1), and methanol
(100%). Altogether seven major fractions were collected, and the elution
of metabolites was monitored by TLC. Further workup (column
chromatography on silica gel) of fraction 1 gave 80 mg (0.36% dry
weight) of aureol (8); fraction 2 gave 45 mg (0.2% dry weight) of 5,6-
dibromo-N,N-dimethyltryptamine. 2′-Des-N-methylaplysinopsin (10, 1.5
mg, 0.0068% dry weight), 6-bromoaplysinopsin (6, 1.2 mg, 0.0054%),
and makaluvamine O (9, 1 mg, 0.0045% dry weight) were obtained
from fractions 3 and 4. Purification of fraction 6 gave thymine (2 mg;
0.009% dry weight) and uracil (3.5 mg; 0.015% dry weight). The
compounds were identified by comparison of their spectral data (1H
NMR,13C NMR, MS) with literature values.
Three kilograms of the frozen sponge V. rigida were extracted four
times with 2000 mL of EtOH in a sonicator. The combined extracts
were filtered and concentrated in vacuo until dried. The crude extract
(211 g) was then subjected to vacuum-liquid chromatography using a
gradient solvent system from hexanes through acetone to methanol,
yielding 20 fractions. The acetone-methanol fraction (1:1) was further
purified by flash column chromatography (C18 cartridge) with a
water–methanol solvent system, yielding five fractions. Further purifica-
tion of fraction 4 (H2O-MeOH, 1:3) on a HPLC C8column (gradient
from 100% H2O to 100% MeOH) yielded 740 mg (0.35% dry weight)
of 5,6-dibromo-N,N-dimethyltryptamine (1). The compound was iso-
lated as a yellow, amorphous solid and could be purified by repeated
recrystallization from methanol and identified on the basis of1H NMR,
13C NMR, and HRMS spectra. Further workup of the residue of the
same fraction by silica gel preparative thin-layer chromatography
(chloroform-methanol, 8:2) and HPLC (C8 columns, gradient from
water to acetonitile) resulted in isolation of 0.1 mg (0.000047% dry
weight) of makaluvamine O (9) and 0.3 mg (0.00014% dry weight) of
arborescidine C (5), identified with high-resolution mass spectrometry
and1H NMR analysis. Purification of fraction 3 on HPLC (C8column,
water to acetonitrile solvent gradient system) yielded 3 mg (0.00142%
dry weight) of 5-bromo-N,N-dimethyltryptamine (2). The presence of
this compound was confirmed with1H NMR,13C NMR, and HRMS.
A fraction eluted with 100% MeOH from the VLC silica column
after further purification on a C18column yielded five fractions; further
workup on the water and MeOH fraction yielded 32.5 mg (0.0154%
dry weight) of aplysinopsin (3), identified by comparison of the spectral
data (1H NMR,13C NMR, HRMS) with literature values. Purification
of the same fraction resulted in isolation of 1 mg (0.00047% dry weight)
of 5,6-dibromoabrine (7) and 6-bromoaplysinopsin (6, 2.0 mg, 0.00094%
dry weight). The fraction eluted with hexane-acetone (8:2) from VLC
yielded small amounts of ilimaquinone (4, 5 mg, 0.00236% dry weight)
and 2 mg (0.00094% dry weight) of aureol (8). The presence of these
compounds was confirmed by TLC, MS, and NMR analysis, comparing
Six kilograms (wet weight) of the frozen sponge S. cerebriformis
was extracted exhaustively with EtOH in a sonicator. The combined
extracts were filtered and concentrated in vacuo until dried. The crude
extract (260 g) was then subjected to vacuum-liquid chromatography
using a gradient solvent system from hexanes through acetone to
methanol, yielding 20 fractions. Nonpolar fractions after purification
yielded 2.5 g (0.9615% dry weight) of ilimaquinone (4), which was
identified by comparison of
standard. Fractions eluted with methanol showed a characteristic
1H NMR and
13C NMR data with a
Figure 3. Effect of compounds 3 (AP), 2 (BDT), and 4 (ili-
maquinone) in (A) forced swim test and (B) locomotor activity
test in male Swiss Webster mice. *p < 0.05 and ***p < 0.001
versus corresponding vehicle.
Journal of Natural Products, 2008, Vol. 71, No. 2Kochanowska et al.
pattern of a dibrominated compound, and the HRMS comparison
with a standard revealed the presence of 5,6-dibromo-N,N-dimeth-
Locomotor Activity and the Forced Swim Test. To evaluate the
isolated compounds for antidepressant-like activity, male Swiss Webster
mice (Harlan, Indianapolis, IN) (25–30 g weight) were used. Animals
were housed in groups of five with a 12 h light/12 h dark cycle. Food
and water were provided ad libitum. All procedures involving animals
were performed as approved by the Institutional Animal Care and Use
Committee of The University of Mississippi. Animals were randomly
divided into groups (n ) 6-10/group). Each group was injected ip
with either the compound (1–20 mg/kg), desipramine (20 mg/kg), or
vehicle (saline, 10% ethanol, or 10% ethanol/1% DMSO). Following
injection, locomotor activity was monitored using an automated activity
monitoring system (San Diego Instruments, San Diego, CA). Each
mouse was placed in a Plexiglas enclosure, and locomotor activity was
recorded as the number of photobeam interruptions for 30 min after
drug injection. The activity for the last 10 min was quantified and
analyzed. Immediately at the end of the locomotor session, individual
mice were subjected to the forced swim test. The mice were individually
placed in a clear plastic cylinder (23 cm high, 10 cm internal diameter)
filled with deionized water (8 cm high) at 25 °C. The mice were
recorded with a video camera (positioned at about 30 cm above the
cylinder) for a total of 6 min. The total period of immobility during
the last 4 min was timed by three independent observers. The mean
immobility time was then calculated. A mouse was judged to be
immobile when it remained afloat, making only minimal movements
to keep its head above water.22
Chick Anxiety-Depression Continuum Test.
white-leghorn cockerels (Cal-Maine W36) were tested at ages 5–6 days
posthatch. Chicks were placed in isolation into a six-unit sound-
attenuating apparatus containing video cameras and microphones 15
min after receiving ip injections of vehicle or 10, 20, or 30 mg/kg 5,6-
dibromo-N,N-dimethyltryptamine. Vocalizations were recorded in 5 min
blocks over a 120 min test period. The anxiety phase of the model is
characterized by high rates of distress vocalizations during the first 5
min of the test period. The depression phase of the model is
characterized by a reduced (approximately 50% of the initial rate) and
stable rate of distress vocalizations during the 30–120 min period of
the test session. All animal procedures were performed by the guidelines
approved by the Institutional Animal Care and Use Committee.
Statistical Analysis. For the forced swim test, immobility times of
the three independent raters were averaged for each mouse, and data
were analyzed using one-way analysis of variance (ANOVA) followed
by Bonferroni multiple comparison post hoc tests to determine statistical
differences from the corresponding vehicle control. Chick distress
vocalization data were analyzed by two-way repeated measures
ANOVA, one-way ANOVA, and simple effects analyses with post hoc
comparisons conducted using Fisher’s LSD test. p-Values less than
0.05 were considered statistically significant.
Acknowledgment. The authors are grateful to Mr. J. Diers for testing
5,6-dibromo-N,N-dimethyltryptamine in the FST. This work was funded
by NIH grants NCRR P20 RR021929 (Center of Research Excellence
in Natural Products Neuroscience); NIAID 5RO1AI1036596; and an
NIH research facilities improvement grant C06 RR-14503-01. NOAA
is gratefully acknowledged for supporting the marine collections in Key
Largo, Florida. Research was conducted pursuant to the Florida Fish
and Wildlife Conservation Commission Division of Marine Fisheries
Management Special Activity License (Scientific Research Activities).
Supporting Information Available: Table showing key field and
histological characteristics of the three sponge species. This information
is available free of charge via the Internet at http://pubs.acs.org.
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