Synapse (New York, N.Y.)
December 1, 2005
Matthew D Schmidt, Mark S Schmidt, Eduardo R Butelman et al.
85 citations
Salvinorin A, a potent hallucinogen from Salvia divinorum, is rapidly eliminated from the body after intravenous administration in rhesus monkeys, with an average elimination half-life of about 57 minutes. Pharmacokinetic differences in distribution half-life, elimination half-life, and area under the curve were observed between males and females, suggesting potential sex differences in the drug's effects. The presumed major metabolite, salvinorin B, was not detected in the study, though it is known to accumulate outside the body.
Synapse (New York, N.Y.)
August 1, 2009
Philip Seeman, Hong-Chang Guan, Hélène Hirbec
83 citations
Phencyclidine and other hallucinogens and psychostimulants can activate dopamine D2 receptors in rat brain tissue, contrary to some earlier reports. Using rat striatum homogenates, phencyclidine achieved 46% of the maximum stimulation produced by dopamine, with a half-maximum concentration of 70 nM. Other compounds, including LSD, salvinorin A, R-modafinil, ketamine, and dizocilpine, also stimulated D2 receptors at concentrations related to their behavioral effects. The stimulation was blocked by a D2 antagonist and by hypertonic buffer containing sodium chloride, which may explain why previous studies failed to observe this effect.
Synapse (New York, N.Y.)
March 1, 2025
Yang Wang, Jesper L Kristensen, Kristi A Kohlmeier
5 citations
The synthetic psychedelic 25CN-NBOH, which binds strongly to serotonin type 2A receptors, has a dual effect on neurons in the mouse medial prefrontal cortex. Acute application of a high concentration (10 µM) increased the frequency of spontaneous excitatory postsynaptic currents, an effect dependent on serotonin 2A receptor activation and not seen with chronic exposure or a lower concentration (200 nM). However, both concentrations suppressed the firing rate of pyramidal neurons after acute and one-hour exposure. This suppression was independent of serotonin 2A receptors but mediated by M-current channels, as blocking M-currents reversed it. The compound thus enhances excitatory transmission while reducing overall excitability, revealing complex cellular actions that may underlie its therapeutic effects.
Synapse (New York, N.Y.)
January 1, 2025
Yiru Dong, Chiye Aoki
2 citations
Anorexia nervosa (AN) has no approved medication and a high relapse rate, especially among adult women. Ketamine infusions have been linked to sustained remission in some adult women with severe AN, and prior mouse studies showed ketamine reduced vulnerability to activity-based anorexia (ABA) in adolescent mice. This experiment tested ketamine in adult female mice undergoing three ABA cycles. Severe weight loss during the third cycle occurred in 89% of control mice but only 69% of ketamine-treated mice. Ketamine significantly reduced overall daily wheel running during the second ABA cycle, including during food availability, and this reduction persisted into the third cycle 10–13 days later. Food intake was not significantly changed. Ketamine may reduce relapse vulnerability in adult females by curbing excessive activity.
Synapse (New York, N.Y.)
July 1, 2024
Simone Larsen Bærentzen, Jakob Borup Thomsen, Majken Borup Thomsen et al.
1 citation
Acute administration of S-ketamine, a fast-acting antidepressant, did not alter dopamine transporter (DAT) availability in the striatum of healthy female rats, as measured by [18F]FE-PE2I PET imaging and [3H]GBR-12935 autoradiography. This negative result suggests that changes in DAT binding are not involved in S-ketamine's rapid antidepressant mechanism, though further research is needed.
Synapse (New York, N.Y.)
November 1, 2025
Oliver H Miller, Nils Grabole, Isabelle Wells et al.
A single low dose of ketamine rapidly lifts mood in people with treatment-resistant depression, with effects lasting up to a week. To understand how, researchers mapped the complete set of proteins being made in the mouse prefrontal cortex after a ketamine dose. They found that ketamine broadly turns on protein synthesis, especially in pathways related to cell signaling, metabolism, blood vessel growth, and structural brain changes. One gene, VIPR2, which makes a receptor for a brain peptide, stood out. This receptor appears only on a specific type of inhibitory neuron. Activating that receptor with a drug changed how nearby brain cells fired and disrupted their coordinated activity, yet it still produced an antidepressant effect in mice, suggesting a new target for depression treatments.
Synapse (New York, N.Y.)
July 1, 2006
Juan Liu, Toshihito Suzuki, Tatsunori Seki et al.
Repeated injections of phencyclidine (PCP, 7.5 mg/kg) in rats cause a 23% decrease in the number of newly born cells in the dentate gyrus of the hippocampus 24 hours after the last injection, but cell counts return to normal within one week. The survival of cells already formed is not affected. PCP also produces stereotyped behaviors that increase with repeated doses, while ataxia and backpedaling behaviors decrease. These transient disruptions in cell proliferation may relate to behavioral abnormalities induced by PCP, though whether they contribute to behavioral sensitization or result from adaptation to the drug's effects remains unclear.
Synapse (New York, N.Y.)
December 15, 2005
Philip Seeman, Mercedes Lasaga
Phencyclidine, a psychotomimetic drug often used to model psychosis, directly activates dopamine D2 receptors, consistent with the dopamine hypothesis of psychosis. In rat cultured anterior pituitary cells, phencyclidine inhibited prolactin release by 50% at a concentration of 4 nM, indicating a potent dopamine-like agonist effect. This finding suggests that phencyclidine's psychotomimetic action may involve direct functional effects on dopamine receptors, rather than solely through glutamate pathways.
Synapse (New York, N.Y.)
August 1, 1991
H C Akunne, A A Reid, A Thurkauf et al.
The brain contains two types of PCP binding sites: site 1 (linked to the NMDA receptor) and site 2 (linked to the dopamine reuptake complex). This work examined brain membranes from multiple species and found detectable site 2 in guinea pig, rabbit, pig, mouse, sheep, and human, but not in rat or chicken. In human cortex, site 2 was the predominant binding site. Dopamine and serotonin uptake inhibitors produced a wash-resistant inhibition of [3H]TCP binding to site 2 but not site 1. The results suggest human cortex possesses high-affinity PCP binding sites associated with biogenic reuptake binding sites, and that guinea pig, but not rat, may be an appropriate animal model for studying PCP site 2 in human brain.