Journal of Neuroscience
April 15, 1997
Bita Moghaddam, Barbara W. Adams, Anita Verma et al.
1,813 citations
Low doses of the NMDA receptor antagonist ketamine (10, 20, and 30 mg/kg) increase glutamate outflow in the rat prefrontal cortex (PFC), suggesting enhanced glutamatergic neurotransmission at non-NMDA receptors. An anesthetic dose (200 mg/kg) decreases glutamate levels, while an intermediate dose (50 mg/kg) has no effect. Ketamine at 30 mg/kg also increases dopamine release in the PFC, an effect blocked by intra-PFC application of the AMPA/kainate receptor antagonist CNQX. Systemic pretreatment with the AMPA/kainate receptor antagonist LY293558 ameliorates ketamine-induced dopamine release and impairment of spatial delayed alternation, a PFC-sensitive cognitive task. Ketamine may disrupt PFC dopaminergic neurotransmission and cognitive functions partly by increasing glutamate release and stimulating postsynaptic non-NMDA glutamate receptors.
Journal of Neuroscience
February 29, 2012
Jesse Wood, Yunbok Kim, Bita Moghaddam
164 citations
Schizophrenia is thought to be a disorder of neural coordination, not cellular pathology. In rats, three different psychotomimetic drugs—MK801 (an NMDA receptor antagonist), DOI (a serotonergic hallucinogen), and amphetamine—all disrupted population activity and modulated gamma oscillations in the prefrontal cortex, but through different mechanisms. MK801 increased population activity, DOI decreased it, and amphetamine had little effect. All three drugs reduced correlations between spike-rate and local field potential power specifically in the gamma band, suggesting they disconnect spike-discharge from gamma oscillators. Gamma oscillations support cognitive functions affected in schizophrenia, offering insight into cortical processing deficits.
Neuropsychopharmacology
February 20, 2023
Gabriela Garza, Bita Moghaddam, Alejandro Torrado Pacheco et al.
69 citations
Acute psilocybin robustly improves cognitive flexibility in male and female rats, enhancing their ability to switch between previously learned strategies in response to uncued environmental changes. Psilocybin did not affect Pavlovian reversal learning, indicating its cognitive effects are selective to strategy switching. The serotonin 5HT2A receptor antagonist ketanserin blocked psilocybin's effect on set-shifting, while a 5HT2C-selective antagonist did not; ketanserin alone also improved set-shifting performance, suggesting a complex pharmacological relationship. The psychedelic DOI impaired cognitive flexibility in the same task, showing this effect does not generalize to all serotonergic psychedelics. These findings provide a behavioral model for investigating psilocybin's neuronal effects relevant to its clinical outcomes.
Neurobiology of learning and memory
September 1, 2024
David S Jacobs, Alina P Bogachuk, Chloé L Le Moing et al.
4 citations
Psilocybin alters how rats suppress actions when facing a conflict between seeking reward and avoiding punishment, but the effect depends on timing. During learning, psilocybin increased behavioral suppression in female rats as they learned that a risky action could lead to punishment. After the reward-punishment associations were already learned, psilocybin decreased behavioral suppression in both male and female rats. These divergent effects suggest that psilocybin's influence on approach-avoidance conflict changes depending on whether the conflict is being learned or has already been learned, which may relate to its therapeutic action in mood disorders.
The Journal of clinical investigation
June 17, 2024
Alejandro Torrado Pacheco, Bita Moghaddam
3 citations
Psilocybin, MDMA, and ketamine show promise for rapidly treating mood and related psychiatric disorders. Clinical data for psilocybin and MDMA, with positive outcomes for depression, anxiety, PTSD, and substance use disorders, have always involved clinician-assisted intervention. Even ketamine's first successful psychiatric use for depression combined it with psychotherapy, and emerging evidence indicates that the subjective experience during ketamine treatment predicts clinical outcome. This review examines how the context and process of drug administration have been integral to published work, stresses the need for trials comparing drug alone versus drug with psychological support, and suggests future animal models that consider context, experience, and expectancy in drug effects.