Selective irreversible blockade of 5-hydroxytryptamine1A and 5-hydroxytryptamine1C receptor binding sites in the rat brain by 8-MeO-2'-chloro-PAT: a quantitative autoradiographic study.

Abstract The possible irreversible blockade of 5-hydroxytryptamine 1 receptor subtypes 5-hydroxy-tryptamine A , 5-hydroxytryptamine 1B /5-hydroxytryptamine 1D and 5-hydroxytryptamine 1C by the chloramine 8-methoxy-2-( N -′2-chloropropyl, N -propyl)aminotetralin (8-MeO-′2-chloro-PAT) was investigated in rat brain sections by quantitative autoradiography using [ 3 H]8-hydroxy-2-(di- n -propylamino) tetralin ([ 3 H]8-OH-DPAT), [ 3 H]5-hydroxytryptamine, [ 125 I]BH-8-MeO-N-PAT and [ 3 I]cyanopindolol as radioligands. A marked reduction (−50% to −75%) of [ 3 H]8-OH-DPAT and [ 3 I]BH-8-MeO-N-PAT specific binding to 5-hydroxytryptamine 1A sites in the hippocampus (CA 1 area) and the dorsal raphe nucleus, and of [ 3 H]5-hydroxytryptamine specific binding to 5-hydroxytryptamine 1C sites in the choroid plexus was found in sections exposed to 1 μM 8-MeO-′2-chloro-PAT and then washed extensively. In contrast the specific binding of [ 3 H]5-hydroxytryptamine to 5-hydroxytryptamine 1B /5-hydroxytryptamine 1D sites and of [ 3 I]cyanopindolol to 5-hydroxytryptamine 1B sites in the substantia nigra and dorsal subiculum remained unaltered by this treatment. Similarly [ 125 I]cyanopindolol binding to β-adrenergic receptors was not affected by 8-MeO-′2-chloro-PAT. Prior occupancy of 5-hydroxytryptamine 1A sites by 10μM 5-hydroxytryptamine or 8-OH-DPAT, and of 5-hydroxytryptaminen 1c sites by 10μM 5-hydroxytryptamine prevented any subsequent blockade by 8-MeO-′2-chloro-PAT. These data indicate that 8-MeO-′2-chloro-PAT should be a useful alkylating agent for achieving selective irreversible blockade of central 5-hydroxytryptamine 1A and 5-hydroxytryptaminen 1c receptors in vivo in the rat.