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Langer SZ, Moret C. 
“Citalopram Antagonizes The Effects Of Lsd On The Presynaptic Serotonin Autoreceptors In Slices Of The Rat Hypothalamus”. 
Brit.J.Pharmacol.. 1982;76.
In the slices of rat occipital cortex, inhibition of neuronal uptake of noradrenaline by cocaine or desipramine reduces the presynaptic effects of alpha2-adrenoceptor agonists of the imidazoline type such as oxymetazoline and clonidine (Pelayo et al., 1980). The presence of presynaptic 5HT inhibitory autoreceptors has been shown in cerebral cortex slices (Guthert and Weinheimer, 1979; Baumann and Waldmeier, 1981) and in synaptosomes of the rat hypothalamus (Cerrito and Raiteri, 1979). We have recently shown that LSD is a potent agonist at presynaptic 5HT autoreceptors in the rat hypothalamus (Larger and Moret - submitted). The aim of the present experiments was to examine the interaction between citalopram, a selective 5HT uptake blocker, and the inhibition by LSD of H-5HT release elicited by electrical stimulation. The experiments were carried out in slices of rat hypothalamus prelabelled with H-5HT. Each slice was stimulated twice at 3 Hz for 2 min (2 msec duration, 20 mA). The overflow elicited by electrical stimulation was entirely calcium dependent. In the controls, the percentage of total tissue radioactivity released was 1.89 + 0.25 during the first period of electrical stimulation (S1) and 1.89 + 0.21 in S2 (n - 7). Expressed as the ratio between two consecutive periods of electrical stimulation the value S2/S was 1.03 + 0.06 (n- 7). Exposure to LSD before S2 reduced sigulficantly he stimulation-evoked overflow of the trittated transmitter (S2/S : 0.62 + 0.11, at 0.01 M, n 8 S2/S1 : 0.32 + 0.07, at 0.1 nM, n =7; and S2/S1 : 0.19 + 0.06, at 1 mcM, n=7). The 5HT receptor blocking agent, methiothepin, antagonized competitively the inhibition by LSD of H-5HT release elicited by electrical stimulation indicating that LSD stimulates presynaptic 5HT autoreceptos. Exposure to 0.01, 0.1 or l mcM of citalopram before S2 did not modify H-transmitter overflow. Under these experimental conditions, citalopram at 0.1 and 3 mcM completely an"agonized the inhibition by LSD (0.01 ; 0.1 and 1 mcM) of H-5HT release elicited by electrical stimulation. When citalopram 0.0 mcM was used, the inhibitory effect of LSD was significantly reduced but not completely antagonized. It is concluded that citalopram, in concentrations in which it does not affect per se the electrically-evoked release of H-5HT, antagonizes the inhibition of neurotransmission induced by the 5HT agonist LSD. The presynaptlc 5HT autoreceptor differs pharmacologically from both the 5HT1 and the 5HT2 subtypes of receptors (Mores and Langer - submitted). Yet the interaction between citalopram and LSD at the level of the 5HT autoreceptor doea not seem to involve a competitive interaction at the same receptor site. One possible explanation of our results is that there is a specific interaction between inhibition of neuronal uptake of 5HT and the presynaptic 5HT autoreceptor. It is tempting to speculate that neuronal uptake of 5HT and the presynaptic 5HT autoreceptor may be linked in a functional manner.
Notes # : (Proc.Suppl.)
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