Matt the Raver
Bluelighter
- Joined
- Oct 7, 2006
- Messages
- 50
fastandbulbous said:
Sounds a bit like a model for 'graceful degradation'.
-
N&PD Moderators: Skorpio | someguyontheinternet
Ketamine: loss of effects means brain damage?
- Thread starter ~_Hiss_~
- Start date
Sounds a bit like a model for 'graceful degradation'.
leungkachong
Bluelighter
I always thought I'm an atypical case for this (and also think that the role of LTP/LTD in learning is not something that we can apply in such a direct manner to cognitive function; just cuz it's the only way we can 'measure' it, it doesn't mean it's integral to it's functioning) because I actually have utilized ketamine as a STUDY AID. I'm actually able to employ (associative) memory extremely effectively. I have used the drug (not mainly in this way until recently) on and (less) off in varying amounts (up to and over .5 gram daily) by insufflation, IM, and IV for 2 years+ now.
And thank god when you have to remember too many things (for neurophysiology) like which layers in premotor cortex innervate the which areas in the motor cortex and how they use pallaidal cells to offer inhibition using blahblah blah and with the efferents running contralaterally on the spinoreticular tract blah blah to a neuromuscular junction... and so on ad absurdum.
And thank god when you have to remember too many things (for neurophysiology) like which layers in premotor cortex innervate the which areas in the motor cortex and how they use pallaidal cells to offer inhibition using blahblah blah and with the efferents running contralaterally on the spinoreticular tract blah blah to a neuromuscular junction... and so on ad absurdum.
Have you read these papers?
Serotonergic agents that activate 5HT2A receptors prevent NMDA antagonist neurotoxicity.
Farber NB, Hanslick J, Kirby C, McWilliams L, Olney JW.
Neuropsychopharmacology. 1998 Jan;18(1):57-62.
Phencyclidine, ketamine, and other agents that block NMDA glutamate receptors trigger a schizophrenia-like psychosis in humans and induce pathomorphological changes in cerebrocortical neurons in rat brain. Accumulating evidence suggests that a complex network disturbance involving multiple transmitter receptor systems is responsible for the neuronal injury, and it is proposed that a similar network disturbance is responsible for the psychotomimetic effects of NMDA antagonists, and might also be involved in the pathophysiology of schizophrenia. In the present study we present evidence that serotonergic agents possessing 5HT2A agonist activity prevent NMDA antagonist neurotoxicity in rat brain. It is proposed that 5HT2A agonists may also prevent the psychotomimetic effects of NMDA antagonists. Among the 5HT2A agonists examined and found to be neuroprotective are LSD and related hallucinogens. The apparent contradiction in proposing that these agents might have antipsychotic properties is resolved by evidence linking their hallucinogenic activity to agonist action at 5HT2C receptors, whereas antipsychotic activity would be attributable to agonist action at 5HT2A receptors.
https://rikki.fi/tajkor/psych/Serot...ors_prevent_NMDA_antagonist_neurotoxicity.pdf
Potentiation of DOM-induced stimulus control by non-competitive NMDA antagonists: a link between the glutamatergic and serotonergic hypotheses of schizophrenia.
Winter JC, Doat M, Rabin RA.
Life Sci. 2000 Dec 8;68(3):337-44.
The present investigation examined the interaction between 2,5-dimethoxy-4-methylamphetamine [DOM] and non-competitive NMDA antagonists in rats trained with DOM [0.6 mg/kg; 75 min pretreatment time] as a discriminative stimulus. Pretreatment with phencyclidine [PCP] at a dose of 3 mg/kg shifted the DOM dose-response relationship to the left. When a fixed dose of DOM [0.1 mg/kg] which by itself yielded 32% DOM-appropriate responding was combined with a range of doses of PCP, dizocilpine, and ketamine, DOM-appropriate percentages increased to maxima of 73%, 84%, and 79%, respectively. When given alone, PCP, dizocilpine, and ketamine were followed by maxima of 36%, 15%, and 13%, respectively. It is concluded that the effects of DOM as a discriminative stimulus are potentiated by pretreatment with non-competitive antagonists of glutamate receptors of the NMDA subtype. These data suggest that the application of the technique of drug-induced stimulus control may prove useful in the reconciliation and integration of current hypotheses as to the etiology of psychotic disorders.
https://rikki.fi/tajkor/psych/Poten...ntrol_by_non-competitive_NMDA_antagonists.pdf
Antagonism of a PCP drug discrimination by hallucinogens and related drugs.
West WB, Lou A, Pechersky K, Chachich ME, Appel JB.
Neuropsychopharmacology. 2000 Jun;22(6):618-25.
Drugs such as PCP and MK-801 can cause psychotic reactions in humans by antagonizing NMDA receptors. This action is ultimately toxic to certain cortical neurons and may be one mechanism underlying neurodegenerative diseases, including schizophrenia. It has been reported that hallucinogens such as LSD, DOM, and DOI can block the neurotoxic effects of NMDA antagonists, possibly by activating inhibitory 5-HT2A receptors on GABAergic interneurons that normally inhibit glutamatergic projections to the retrosplenial and cingulate cortexes. The purpose of this experiment was to determine the extent to which similar drugs might also alter the behavioral effects of one NMDA antagonist, PCP. Rats were trained to discriminate this compound (2.5 mg/kg) from saline and were then given a series of antagonist tests. It was found that LSD (0.32 mg/kg) and DOM (4.0 mg/kg) blocked the PCP cue completely; DMT (8.0 mg/kg) and a structural congener of LSD, lisuride (LHM; 0.4 mg/kg), blocked the effects of PCP partially. The 5-HT/DA antagonists spiperone and ritanserin had no effect on the PCP cue. These data suggest that LSD, DOM, and, less effectively, DMT and LHM can block the behavioral as well as the neurotoxic effects of NMDA antagonists most likely through agonist actions at 5-HT2 receptors.
https://rikki.fi/tajkor/psych/Antag...nation_by_Hallucinogens_and_Related_Drugs.pdf
Serotonergic agents that activate 5HT2A receptors prevent NMDA antagonist neurotoxicity.
Farber NB, Hanslick J, Kirby C, McWilliams L, Olney JW.
Neuropsychopharmacology. 1998 Jan;18(1):57-62.
Phencyclidine, ketamine, and other agents that block NMDA glutamate receptors trigger a schizophrenia-like psychosis in humans and induce pathomorphological changes in cerebrocortical neurons in rat brain. Accumulating evidence suggests that a complex network disturbance involving multiple transmitter receptor systems is responsible for the neuronal injury, and it is proposed that a similar network disturbance is responsible for the psychotomimetic effects of NMDA antagonists, and might also be involved in the pathophysiology of schizophrenia. In the present study we present evidence that serotonergic agents possessing 5HT2A agonist activity prevent NMDA antagonist neurotoxicity in rat brain. It is proposed that 5HT2A agonists may also prevent the psychotomimetic effects of NMDA antagonists. Among the 5HT2A agonists examined and found to be neuroprotective are LSD and related hallucinogens. The apparent contradiction in proposing that these agents might have antipsychotic properties is resolved by evidence linking their hallucinogenic activity to agonist action at 5HT2C receptors, whereas antipsychotic activity would be attributable to agonist action at 5HT2A receptors.
https://rikki.fi/tajkor/psych/Serot...ors_prevent_NMDA_antagonist_neurotoxicity.pdf
Potentiation of DOM-induced stimulus control by non-competitive NMDA antagonists: a link between the glutamatergic and serotonergic hypotheses of schizophrenia.
Winter JC, Doat M, Rabin RA.
Life Sci. 2000 Dec 8;68(3):337-44.
The present investigation examined the interaction between 2,5-dimethoxy-4-methylamphetamine [DOM] and non-competitive NMDA antagonists in rats trained with DOM [0.6 mg/kg; 75 min pretreatment time] as a discriminative stimulus. Pretreatment with phencyclidine [PCP] at a dose of 3 mg/kg shifted the DOM dose-response relationship to the left. When a fixed dose of DOM [0.1 mg/kg] which by itself yielded 32% DOM-appropriate responding was combined with a range of doses of PCP, dizocilpine, and ketamine, DOM-appropriate percentages increased to maxima of 73%, 84%, and 79%, respectively. When given alone, PCP, dizocilpine, and ketamine were followed by maxima of 36%, 15%, and 13%, respectively. It is concluded that the effects of DOM as a discriminative stimulus are potentiated by pretreatment with non-competitive antagonists of glutamate receptors of the NMDA subtype. These data suggest that the application of the technique of drug-induced stimulus control may prove useful in the reconciliation and integration of current hypotheses as to the etiology of psychotic disorders.
https://rikki.fi/tajkor/psych/Poten...ntrol_by_non-competitive_NMDA_antagonists.pdf
Antagonism of a PCP drug discrimination by hallucinogens and related drugs.
West WB, Lou A, Pechersky K, Chachich ME, Appel JB.
Neuropsychopharmacology. 2000 Jun;22(6):618-25.
Drugs such as PCP and MK-801 can cause psychotic reactions in humans by antagonizing NMDA receptors. This action is ultimately toxic to certain cortical neurons and may be one mechanism underlying neurodegenerative diseases, including schizophrenia. It has been reported that hallucinogens such as LSD, DOM, and DOI can block the neurotoxic effects of NMDA antagonists, possibly by activating inhibitory 5-HT2A receptors on GABAergic interneurons that normally inhibit glutamatergic projections to the retrosplenial and cingulate cortexes. The purpose of this experiment was to determine the extent to which similar drugs might also alter the behavioral effects of one NMDA antagonist, PCP. Rats were trained to discriminate this compound (2.5 mg/kg) from saline and were then given a series of antagonist tests. It was found that LSD (0.32 mg/kg) and DOM (4.0 mg/kg) blocked the PCP cue completely; DMT (8.0 mg/kg) and a structural congener of LSD, lisuride (LHM; 0.4 mg/kg), blocked the effects of PCP partially. The 5-HT/DA antagonists spiperone and ritanserin had no effect on the PCP cue. These data suggest that LSD, DOM, and, less effectively, DMT and LHM can block the behavioral as well as the neurotoxic effects of NMDA antagonists most likely through agonist actions at 5-HT2 receptors.
https://rikki.fi/tajkor/psych/Antag...nation_by_Hallucinogens_and_Related_Drugs.pdf
Dondante
Bluelighter
- Joined
- Dec 6, 2005
- Messages
- 1,638
Matt the Raver said:
So it looks from the papers above that ketamine, which causes NMDA receptor hypofunction, is neurotoxic because it prevents inhibitory neurons (GABAergic and noradrenergic) from performing their normal function. The result is disinhibition of certain excitatory pathways, which results in excitotoxicity of neurons that are no longer adequately inhibited. Of course, this is in the rat brain. Can someone remind me why Olney's lesions probably don't occur in humans? Is it just because the dosage used in the studies was extremely high, or does it have to do with rat neurophysiology?
drunken_etard
Bluelighter
haha i was talking about this exact same article on erowids last night whikle high on 75mgs of Ketamine.