CC BY
409th multidisciplinary international
Conference of Biological Psychiatry
«Stress and Behavior»
Proceedings of the 9th International Multidisciplinary Conference «Stress and behavior» Saint-Petersburg, Russia, 16-19 May 2005 Editor: Allan V. Kalueff, PhD
CONFERENCE ABSTRACTS
5. PSYCHONEUROIMMUNOLOGY
THE EFFECT OF INTERLEUKIN-1 BETA ON ALCOHOL INTAKE IN RATS WITH DIFFERENT ETHANOL PREFERENCE
S.V. Nikolaev, O.E. Zubareva, A.A. Lebedev, V.M. Klimenko, P.D. Shabanov
Medical Military Academy, Institute for Experimental Medicine, St. Petersburg, Russia
Recent experimental findings on addictive behavior indicate that cytokines — endogenous mediators of neuro-immunological interactions — may be involved in addiction. Interleukin-1 beta (I1-1beta) is not only a key factor of the immune system mobilization, but also affects the CNS (Lacosta et al., 1998). I1-1beta and its receptors are found in hypothalamus and other structures related to the regulation of incentive behavior. Administration of I1-1beta alters activity of brain monoaminergic systems, contributing to alcoholism and drug addiction pathogenesis. Given that stress is indisputable regulator of reinforcing processes, we can suggest the reward properties may be modified by I1-1beta, whose activation is known to be a marker and perhaps an acting component of stress (Shintani et al., 1995). On the other hand, it should be noted that animals have various degree of vulnerability to drugs and alcohol. The aim of the present study was to assess the influence of I1-1 beta on alcohol intake in rats with initially different alcohol motivation.
Methods: 80 male Wistar rats were subjected to forced intake of 15% ethanol solution instead of water for 6 months. When exposed to this procedure rats were kept together 9—10 animals per cage. Then for 5 days rats were being moved to individual testing containers with free access to 10% ethanol solution and water. Amount of liquid consumed was measured daily with .5 ml accuracy. For all animals, alcohol fraction in total daily drinking was within two ranges: 0—15% and 40—100%. Respectively, rats demonstrating stable levels of alcohol consumption were divided into «low-consuming» (L) and «high-consuming» (H) groups. On the 4-th experimental day, the animals were injected i.p. with 250 pl saline. Next day they received the same volume of Il-1 beta at pyrogenic dose 1 pg/kg.
Results and discussion: After saline injection, total amount of liquid consumed did not differ in the H and L groups. In contrast, I1-1 beta reduced total liquid intake in the H group (saline: 41 ± 5 ml; I1-1beta: 28±4 ml; p =0.08) and showed a similar tendency in the L group. Particular pattern of alcohol and water consumption was observed after I1-1 beta injection in both groups studied. In the group H, I1-1beta did not influence water consumption, while inhibited significantly intake of ethanol solution. Herewith ethanol preference (measured as alcohol/water ratio) was unaltered by I1-1beta (saline: 0.70 ± .09; I1-1beta: 0.60 ± 0.10; p = 0.2). In turn, the L group demonstrated strong decrease in water consumption accompanied by elevated alcohol intake (saline: 2.50 ± 0.04 ml; I1-1beta: 11.3 ± 0.03 ml; p = 0.01). Altered preference was expressed in a 8-fold increase of alcohol/water ratio (saline: 0.40 ± 0.02; I1-1beta: 0.33 ± 0.10; p = 0.01). These data demonstrate that I1-1beta is able to strongly modify ethanol consumption, and that its effects are contrasting, if not opposite, in animals with high and low alcohol preferences. Complete explanation of this fact requires further studies but some assumptions can be made. It is known that individual vulnerability to self-administer addictive compounds is often related to insufficient activity of mesolimbic dopaminergic system (Shabanov et al., 2002). Ethanol is an activator of dopaminergic system but its long-lasting exposure probably lead to
Psychopharmacol. Biol. Narcol. 2005. Vol. 5, N 2. P. 913-914
Psyhopharmacology & biological narcology
ISSN 1606-8181
disruption of normal reinforcing process in some animals. Thus, animals demonstrating intensive alcohol drinking may be considered «decompensated». There is evidence that I1-1beta increase metabolism of dopamine within nucleus accumbens (Merali et al., 1997). This cytokine, in spite of sickness behavioral response, does not induce anhedonia (Anisman et al., 1998). Therefore, similar to other molecular factors, I1-1beta may substitute ethanol reward, thus making alcohol consumption unnecessary. Increased degree of intake in the initially non-preferring rats may include another aspect of ethanol action, namely its alimentary properties. When food motivation and behavior is inhibited by I1-1 beta, ethanol may serve as an easily accessible and more preferable source of calories. On the other hand, rats preferring ethanol (in addition to impaired motivation) may have disruption of feedback mechanism signaling depletion of energy sources. Finally, additional factor that may influence consumption is aversive ethanol taste and possible modulation of taste perception by I1-1beta.
Conclusion: Il-1 beta, known as an effector of the immune response, is a highly specific modulator of voluntary ethanol ingestion in rats. Reflecting incompletely understood mechanism, administration of I1-1beta affected alcohol consumption depending on initial preference to ethanol. The ability of I1-1b to reduce alcohol intake may assist in further development of new methods to treat alcohol addiction.
Psychopharmacol. Biol. Narcol. 2005. Vol. 5, N 2. P. 913-914
Psyhopharmacology & biological narcology
ISSN 1606-8181
