Introduction
Alcoholism is a complex disease involving several neuro-
transmitter systems. For example, the role of dopamine is
well established but only few studies have explored the role
of histamine in this context [1, 2]. In our previous study we
measured histamine (HA) and tele-methylhistamine (MHA)
from postmortem brains of alcoholics and found that both
HA and MHA concentrations were higher in cortical grey
matter in alcoholics compared to non-alcoholics [2]. Here we
compare HA and MHA levels separately in frontal cortex,
insular cortex, and occipital cortex from alcoholics and non-
alcoholics.
Materials and methods
Human brains were obtained during clinical necropsy from the Depart-
ment of Forensic Medicine, University of Oulu, Finland. This part of the
study was approved by the Ethics Committee of the University of Oulu
and the National Institute of Medicolegal Affairs, Helsinki, Finland.
Postmortem brains of alcoholics and non-alcoholic comparison
subjects were studied. Two physicians, independently, made the diag-
noses. Both hospital and outpatient records were available for all 27 cas-
es. Alcoholics were selected after evident alcohol dependency or harm-
ful use according to diagnostic criteria in DSM-III-R (Diagnostic and
Statistical Manual of Mental Disorders, Revised version). Further sub-
classification into type 1 (n = 10, age 42 – 76 yrs) and type 2 (n = 8, age
18 – 49 yrs) was done according to Cloninger [3]. The main diagnostic
differences between subtypes were early onset of alcohol abuse (before
the age of 25) and documented antisocial behaviour in type 2 alcoholics.
Non-alcoholic subjects (n = 9, age 36– 77 yrs) had no evidence of psy-
chiatric or neurological background. All had died of sudden causes:
acute heart disease (all non-alcoholics), suicide, homicide, pneumonia,
acute alcohol intoxication, acute pancreatitis and subdural hematoma.
Subjects having disorders or medications affecting CNS (such as neu-
roleptics, antidepressants, or anti-epileptics) were excluded from the
study. The brains were divided on the midsagittal plane, and the left
hemisphere was quickly frozen to –75°C. The frozen hemispheres were
sectioned into 100 mm canto-meatal slices with heavy duty microtome.
The sections were stored in –25 °C until use. Samples of frontal cortex,
insular cortex, and occipital cortex were scraped with spatula from the
tissue sections (Fig. 1). Histamine was assayed by HPLC and MHA by
GC-MS [2]. Statistical analyses were performed by Kruskall-Wallis-test
and pairs compared as suggested by Siegel and Castellan [4], p < 0.05
was considered significant.
Results and discussion
In the type 1 alcoholics histamine levels were generally
slightly higher, but the differences were not significant (Fig.
2a). In the type 2 alcoholics, MHA level was significantly
(p < 0.05) higher in all cortical areas when compared to non-
alcoholics (Fig. 2b) but the differences between type 1 and 2
alcoholics were not significant. Histamine turnover, as mea-
sured by MHA/HA ratio, tended to be highest among type 2
alcoholics and the difference was greatest in frontal cortex,
but it did not reach significance. The levels of HA and MHA
were slightly lower in the occipital cortex than in the two oth-
er areas but no significant differences were found. Previous-
ly it has been found that MHA levels tend to increase during
ageing [5]. In this study in the type 2 alcoholics, the opposite
Inflamm. res. 52, Supplement 1 (2003) S37– S38
1023-3830/03/01S37-02
© Birkhäuser Verlag, Basel, 2003
Inflammation Research
Alcoholics show altered histaminergic neurotransmission
in several cortical areas – Preliminary report
K. Alakärppä
1
, E. Tupala
1,2
, T. Mantere
1,2
, T. Särkioja
3
, P. Räsänen
4
, J. Tarhanen
5
, J. Tiihonen and L. Tuomisto
1
1
Department of Pharmacology and Toxicology, University of Kuopio, PO Box 1627, FIN-70211 Kuopio, Finland, Fax: ++ 358 17 162424,
e-mail: kjhyvari@hytti.uku.fi
2
Department of Forensic Psychiatry, University of Kuopio, Niuvanniemi Hospital
3
Department of Forensic Medicine, University of Oulu
4
Department of Psychiatry, University of Oulu
5
Department of Environmental Sciences, University of Kuopio, Finland
Correspondence to: K. Alakärppä
Fig. 1. A canto-meatal section of left hemisphere of human brain. HA
and MHA were measured from the grey matter of frontal, insular and
occipital cortex.