164 Braitt Research, 93 (1975) 164-167 ~('3 Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands LSD and dopamine-sensitive adenylate-cyclase in various rat brain areas P. F. SPANO, K. KUMAKURA*, G. C. TONON, S. GOVONI AND M. TRABUCCHI Institute of Pharmacology and Pharmacognosy, University of Milan and ( M. T.) Institute of Pharma- cology, University of Milan, Milan 20129 (Italy) (Accepted April 14th, 1975) The mechanism or mechanisms by which LSD induces its hallucinogenic effects are not yet understood 1,~,6,7. Biochemical, physiological and behavioral data suggest that LSD interacts at the level of monoaminergic synapses in brain 9,17. Recently Pieri and Pieri 14 have observed that LSD, as apomorphine, induces circling behavior in rats which had been unilaterally injected in the medial forebrain bundle with 5,6-dihydroxytryptamine or 6-hydroxydopamine. The circling behavior induced by LSD or apomorphine in the lesioned rats was blocked by haloperidol, indicating that LSD, like apomorphine, may stimulate directly dopamine (DA) receptors in the striatum. On the other hand, Uzunov and Weiss 19 have described that D-LSD produces an increase of the concentration of cyclic AMP either when incubated in vitro with slices of rat brain stem or in rat brain stem and cerebrum after in vivo administration. Moreover, these authors showed that the neuroleptic trifluoperazine both in vitro and in vivo inhibits the accumulation of cyclic AMP elicited by D-LSD. However, Uzunov and Weiss have left open the question of how D-LSD increased the concentration of cyclic AMP in brain since none of the psychotomimetic drugs they studied altered the activity of either adenylate cyclase or phosphodiesterase in cerebrum, brain stem, cerebellum or pineal gland homogenates. More recently DA-sensitive adenylate-cyclases have been identified in homog- enates of the rat caudate nucleus 10, tuberculum olfactorium 5, nucleus accumbens s and limbic cortex 4. Haloperidol and other antipsychotic neuroleptics antagonize the activation by DA of this enzyme. It was therefore our purpose to investigate whether D-LSD directly and selec- tively stimulates DA-sensitive adenylate-cyclase in striatum and in other areas of the limbic system which appears to be more strictly linked to perception, feeling and emo- tional behavior. Male Charles River rats, weighing 120--150 g, were used in our experiments. * Visiting scientist from the Dept. of Biochemistry, Sophia University, Tokyo, Japan.