mk212 hydrochloride  (R&D Systems)

Journal: Scientific Reports

Article Title: Raphe glucose-sensing serotonergic neurons stimulate KNDy neurons to enhance LH pulses via 5HT2CR: rat and goat studies

doi: 10.1038/s41598-024-58470-4

Figure Lengend Snippet: Central administration of serotonin (5HT) and serotonin-2C receptor (5HT2CR) agonist stimulated GnRH pulse generator activity, and 5HT2CR antagonism blocked the 5HT-induced stimulation of GnRH pulse generator activity recorded by multiple unit activity (MUA) in the ARC of OVX goats. ( a ) Schematic illustration of the experimental procedure for determining the effects of lateral ventricle (LV) administration of 5HT and 5HT2CR agonist and antagonist on MUA volley in goats. 5HT and MK212, a 5HT2CR agonist, were injected into the LV at a half-time of the mean interval of MUA volleys (Tm/2) determined by the 5-h prerecording of MUA. SB206553 (SB), a 5HT2CR antagonist, was infused into the LV immediately after the second MUA volley until the 5HT injection at Tm/2 after the third MUA volley. ( b ) Profiles of MUA volleys and LH pulses in representative goats treated with 5HT or Veh (arrows). Arrow heads indicate the peaks of LH pulses identified by the PULSAR computer program. ( c ) The mean MUA volley interval of OVX goats after central 5HT (0.5 or 5 µmol) administration was significantly ( p < 0.05) shortened compared with that of Veh-treated control goats. ( d ) Percent change in mean LH levels of OVX goats after central 5HT (5 µmol) administration significantly ( p < 0.05) increased compared with that of Veh-treated controls. ( e ) Profiles of MUA volleys and LH pulses of representative goats treated with LV infusion of SB (green) or Veh (gray) and LV injection of 5HT (arrows). ( f ) The mean MUA volley intervals at the postinfusion period were significantly ( p = 0.0026) shortened by 5HT injection in the Veh-treated group (gray), whereas the interval at the postinfusion period significantly ( p = 0.0026) elongated in the SB-treated group (green). In addition, significant differences were found in the MUA volley interval between the SB + 5HT and Veh + 5HT groups during the postinfusion period ( p = 0.0037). ( g ) The percent change in mean LH levels in OVX goats treated with LV infusion of SB (green) or Veh (gray). ( h ) Profiles of MUA volleys and LH pulse of representative OVX goats treated with LV administration of MK212 (0.5 or 5 µmol) or Veh (arrows). ( i ) The mean MUA volley interval of OVX goats treated with central administration of MK212 (5 µmol) was significantly shorter than that of Veh-treated controls ( p = 0.0022). ( j ) The percent change in mean LH levels in OVX goats treated with LV administration of MK212 (0.5 or 5 µmol) or Veh. Values are means ± SEMs. The numbers in each column indicate the number of animals used. Arrowheads indicate the peaks of LH pulses identified by the PULSAR computer program.

Article Snippet: An 18-G stainless steel guide cannula was implanted in the LV for intracerebroventricular administration of serotonin hydrochloride (Sigma‒Aldrich), MK212 hydrochloride (a selective 5HT2CR agonist; R&D Systems), or SB206553 hydrochloride (5HT2B/2CR antagonist; Santa Cruz Biotechnology) as described previously .

Techniques: Activity Assay, Injection, Control

Journal: Behavioural pharmacology

Article Title: Acquisition session length modulates consolidation effects produced by 5–HT 2C ligands in a mouse autoshaping-operant procedure

doi: 10.1097/FBP.0b013e328337bde7

Figure Lengend Snippet: Effects of saline and 5–HT2C ligands on the consolidation of autoshaped-operant reinforced and nonreinforced responding in mice after 1-h (white bars) and 2-h (black bars) acquisitions sessions on day 1. Vertical axis: left panel, mean-adjusted latency defined as the latency to the tenth minus the latency to the first reinforced response; middle panel, rate of overall dipper hole nose-poke responses per second; right panel, rate of left and right nose-poke responding as a measure of nonreinforced activity. Horizonrtal axis: saline, drugs and doses in mg/kg, administered intraperitoneally. 1-h acquisition session: 32 mg/kg mianserin increased day 2 mean latency relative to saline controls (P < 0.001), MK212 (P < 0.01), SB206 553 (P < 0.01), BOL (P < 0.05) and methysergide (P < 0.01) (left panel); reduced rates of reinforced responding relative to saline (P < 0.01) and 10 mg/kg SB206 553 (P < 0.01) (middle panel); MK212 increased nonreinforced response rates relative to 32 mg/kg mianserin (P < 0.05) and methysergide (P < 0.05) (right panel). 2-h acquisition session: 32 mg/kg mianserin increased day 2 mean latency relative to saline controls (P < 0.05) and all other agents tested (P < 0.05) (left panel); reduced rates of reinforced responding compared with saline controls (P < 0.05), m-chlorophenylpiperazine (mCPP) (P < 0.01), 3.2 mg/kg SB206 553 (P < 0.05) and methysergide (P < 0.01) (middle panel); 10 mg/kg SB206 553 significantly altered rates of nonreinforced responding relative to saline controls, (P < 0.05), MK212 (P < 0.01), mCPP (P < 0.05) and 32 mg/kg mianserin (P < 0.05) (right bars). Number of mice tested during the 1- and 2-h acquisition session, respectively: saline (n = 11, 10), MK212 (n = 5, 5), mCPP (n = 11, 12), (10 mg/kg n = 6, 6; 32 mg/kg n = 6, 9), SB206 553 (3.2 mg/kg n = 6, 4; 10 mg/kg n = 11, 5), BOL (n = 5, 7), and methysergide (n = 5, 9). Twelve mice failed to earn five (1 h) or 10 (2 h) reinforcers during the day 1aquisition session. Vertical bars represent SEM *P < 0.05; **P < 0.01; ***P < 0.001.

Article Snippet: Drugs MK212 hydrochloride, mCPP hydrochloride, and methy-sergide maleate (Tocris Bioscience, Ellisville, Missouri, USA), mianserin hydrochloride, SB 206 553 hydrochloride (Sigma Aldrich, St. Louis, Missouri, USA), and BOL (National Institute on Drug Abuse, Bethesda, Maryland, USA).

Techniques: Saline, Activity Assay

Journal: Psychoneuroendocrinology

Article Title: Behavioral, Pharmacological and Neuroanatomical Analysis of Serotonin 2C Receptor Agonism on Maternal Behavior in Rats

doi: 10.1016/j.psyneuen.2016.08.017

Figure Lengend Snippet: Effects of systemic MK212 (2.0 mg/kg) on maternal behavior under 4-h pup-separation (PS, pups were taken away from dams 4 h before the test) and no-pup-separation (NS) conditions on PP 4 and 6. On each test day, maternal behavior was observed for 10 min at 4 time points: 0.5 h before, 0.5, 2 and 4 h after the injection. On PP 4, mother rats were tested under two separation conditions. On PP 6, the rats tested in the pup-separation condition on Day 4 were tested in the no-pup-separation condition, and those previously tested in the no-pup-separation condition were tested in the pup-separation condition. Data from the postpartum day 4 and 6 under the same condition (PS or NS) are combined and expressed as mean ± SEM. A, number of pup retrieved; B, latency of first pup retrieved; C, duration of pup nursing; D, duration of pup licking; E, duration of nest building; F, duration of pup sniffing. ** p < 0.01, * p < 0.05 significantly different between the different drug administrations (VEH vs. MK212) within the same separation condition (PS or NS); ## p < 0.01, # p < 0.05 significantly different between the different separation conditions (PS vs. NS) within the same drug exposure (VEH or MK212).

Article Snippet: MK212 [6-Chloro-2-(l-piperazinyl) pyrazine hydrochloride] and SB242084 [6-Chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridiny]-1H-indole-1-carboxyamide dihydrochloride hydrate] were obtained from Tocris Bioscience (Ellisville, MO, USA).

Techniques: Injection

Journal: Psychoneuroendocrinology

Article Title: Behavioral, Pharmacological and Neuroanatomical Analysis of Serotonin 2C Receptor Agonism on Maternal Behavior in Rats

doi: 10.1016/j.psyneuen.2016.08.017

Figure Lengend Snippet: Effects of systemic MK212 (2.0 mg/kg) on food retrieval under 6-h food-deprivation (FD) and no-food-deprivation (ND) conditions on postpartum day 8 and 10. Each retrieval test lasted 10 min. Number (A) and latency (B) of food retrieval from the postpartum day 8 and 10 under the same condition (FD or ND) are combined and expressed as mean + SEM. * p < 0.05, ** p < 0.01 significantly different between the different drug administrations (VEH vs. MK212) within the same deprivation treatment (FD or ND).

Article Snippet: MK212 [6-Chloro-2-(l-piperazinyl) pyrazine hydrochloride] and SB242084 [6-Chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridiny]-1H-indole-1-carboxyamide dihydrochloride hydrate] were obtained from Tocris Bioscience (Ellisville, MO, USA).

Techniques:

Journal: Psychoneuroendocrinology

Article Title: Behavioral, Pharmacological and Neuroanatomical Analysis of Serotonin 2C Receptor Agonism on Maternal Behavior in Rats

doi: 10.1016/j.psyneuen.2016.08.017

Figure Lengend Snippet: Effects of acute MK212 (2.0 mg/kg) treatment on pup retrieval with pretreatment of SB242084 (0, 0.6, 1.0 mg/kg). SB242084 was injected 10 min before the MK212. Maternal behavior was tested for 10 min at 30 min before, 30 min, 60 min and 24 h after MK212 injection. Number of pups retrieved in each test is expressed as mean + SEM. ** p < 0.01 significantly different between the VEH-1 + VEH and − MK212 groups. # p < 0.05 significantly different between SB242084 + MK212 and VEH-1 + MK212 groups.

Article Snippet: MK212 [6-Chloro-2-(l-piperazinyl) pyrazine hydrochloride] and SB242084 [6-Chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridiny]-1H-indole-1-carboxyamide dihydrochloride hydrate] were obtained from Tocris Bioscience (Ellisville, MO, USA).

Techniques: Injection

Journal: Psychoneuroendocrinology

Article Title: Behavioral, Pharmacological and Neuroanatomical Analysis of Serotonin 2C Receptor Agonism on Maternal Behavior in Rats

doi: 10.1016/j.psyneuen.2016.08.017

Figure Lengend Snippet: Effects of MK212 microinfused into the nucleus accumbens shell (NAs, A) on pup retrieval throughout the four test days (PP 3, 5, 7 and 9). Effects of MK212 microinfused into the medial preoptic area (MPOA, B) or medial prefrontal cortex (mPFC, C) on pup retrieval throughout the four test days (PP 4, 6, 8 and 10). Number of pups retrieval in each test is expressed as mean + SEM.

Article Snippet: MK212 [6-Chloro-2-(l-piperazinyl) pyrazine hydrochloride] and SB242084 [6-Chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridiny]-1H-indole-1-carboxyamide dihydrochloride hydrate] were obtained from Tocris Bioscience (Ellisville, MO, USA).

Techniques:

Journal: Psychoneuroendocrinology

Article Title: Behavioral, Pharmacological and Neuroanatomical Analysis of Serotonin 2C Receptor Agonism on Maternal Behavior in Rats

doi: 10.1016/j.psyneuen.2016.08.017

Figure Lengend Snippet: A c-Fos immunohistochemistry study for the MK212 (2.0mg/kg) effects on maternal behavior. (A) Effects of repeated MK212 administration on the number of pup retrieved. Maternal behavior was tested for 10 min once daily from PP 6 to 9, with starting at 30 min after drug injection. (B) Effects of acute and repeated MK212 administration on c-Fos immunoreactivity. On PP 10, all rats were overdosed and perfused and their brains were extracted for c-Fos immunoreactivity staining 1 h after the drug injection. Number of anti-c-Fos positive cells is expressed as mean + SEM. ** p < 0.01, * p < 0.05 significantly different between the VEH and MK212 in the same regimen (acute or repeated drug exposure); # p < 0.05, ## p < 0.01 significantly different between the acute and repeated drug treatment in the same treatment condition (VEH or MK212). LSv, ventral lateral septum; CeA, central amygdala; MPOA, medial preoptic area; DG, dentate gyrus; DR, dorsal raphe; VTA, ventral tegmental area. (C), photomicrographs of immunohistochemistry showing c-Fos expression in the dorsal raphe. In comparison to the VEH groups, MK212 reduced the number of c-Fos immunoreactive neurons under both acute and repeated administration. (1), acute VEH; (2), acute 2.0mg/kg MK212; (3), repeated VEH; (4), repeated 2.0mg/kg MK212. Scale bar =100 μm.

Article Snippet: MK212 [6-Chloro-2-(l-piperazinyl) pyrazine hydrochloride] and SB242084 [6-Chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridiny]-1H-indole-1-carboxyamide dihydrochloride hydrate] were obtained from Tocris Bioscience (Ellisville, MO, USA).

Techniques: Immunohistochemistry, Injection, Staining, Expressing, Comparison