Phencyclidine-like behavioral effects in pigeons induced by systemic administration of the excitatory amino acid antagonist, 2-amino-5-phosphonovalerate

A selective N-methyl-D-aspartate antagonist, DL-2-amino-5-phosphonovalerate, was found to produce PCP-like catalepsy, discriminative stimulus effects, and stereotyped operant responding in pigeons when administered intramuscularly. These results support the hypothesis that the behavioral effects of PCP-like drugs result at least in part from reduced neurotransmission at excitatory amino acid synapses utilizing N-methyl-D-aspartate preferring receptors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26045/1/0000118.pd

Ambulatory blood pressure monitoring in children: A retrospective single-center study

Objectives(1) Compare 24-hour ambulatory blood pressure monitoring (ABPM) diagnoses in a pediatric population with the new 2022 guidelines to the original diagnoses with the 2014 guidelines. (2) Determine whether findings of hypertension from ABPM could be predicted from prior patient data. (3) Determine whether ABPM readings could predict left ventricular mass index (LVMI) in patients who obtained an echocardiogram (ECHO).Study designSingle-center retrospective study on patients referred to Pediatric Nephrology Clinic for evaluation of elevated blood pressure who underwent ABPM from 2015 to 2018. Predictions of hypertension were obtained using a logistic regression model, and predictions of LVMI were performed using regression models including (a) the wake systolic and diastolic BP indices, or (b) additionally including the standard deviation (SD) of wake SBP and DBP.ResultsWith the change in 2022 to new ABPM guidelines from the AHA, comparing the old and new guidelines led to 70% of previous pre-hypertensive diagnoses now meeting criteria for diagnosis of hypertension, and a rise from 21% of the ABPMs meeting criteria for hypertension to 51% now meeting criteria. In a logistic regression model, prior patient data were not predictive of a diagnosis of hypertension from ABPM (Nagelkerke's R2 = 0.04). Among the individual variables studied, none were statistically significant. For prediction of LVMI, the SD of wake SBP and DBP were significantly associated with increased LVMI, but the wake SBP and DBP indices were not.ConclusionsIn our patient population, the new ABPM guidelines led to a significant increase in diagnoses of hypertension. Prior patient data was not sufficient to predict a diagnosis of hypertension by ABPM, supporting the need for evaluation by ABPM as the gold standard. Our analysis of the relationship between ABPM readings and LVMI supports the hypothesis that BP variability contributes to increased LVMI. These data are consistent with growing evidence in the adult literature that BP variability detected by ABPM is associated with left-ventricular hypertroph

Phencyclidine-like catalepsy induced by the excitatory amino acid antagonist DL-2-amino-5-phosphonovalerate

This study presents experimental evidence for the mediation of a behavioral effect of phencyclidine-like drugs by inhibition of neurotransmission at excitatory synapses utilizing N-methyl-aspartate (NMA) receptors by showing that -2-amino-5-phosphonovalerate, a selective NMA antagonist, produces phencyclidine-like catalepsy in pigeons. This finding suggests the possibility that other behavioral actions of phencyclidine-like substances may be mediated in a similar fashion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26248/1/0000328.pd

Phencyclidine (PCP)-like discriminative stimulus effects of metaphit and of 2-amino-5-phosphonovalerate in pigeons: generality across different training doses of PCP

Pigeons were trained to discriminate either a fixed dose of PCP (1 mg/kg; n =3) or a progressively decreasing dose (1-0.56–0.32 mg/kg; n =4) from saline. Lowering of the training dose shifted the dose-effect curve for PCP's discriminative stimulus effects about 5-fold to the left, in a parallel manner, but did not decrease the accuracy of the discrimination performance and did not significantly increase the extent to which pentobarbital and chlordiazepoxide produced PCP-appropriate responding. Dose-effect curves based on binary generalization data were evaluated statistically with new methods that may be more appropriate than those used previously. Metaphit, a proposed PCP-receptor acylator, and 2-amino-5-phosphonovalerate (AP5), an N-methyl- d -aspartate (NMDA) antagonist, produced complete PCP-appropriate responding in the high training dose group only at doses that suppressed the rate of responding and that produced ataxia. However, 4-fold lower doses of metaphit and AP5, which did not produce directly observable behavioral effects, were found to substitute completely for PCP in the low training dose group. These data support the notion that PCP, metaphit, and AP5 have a common discriminative effect in pigeons.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46447/1/213_2004_Article_BF00207232.pd

Excitatory amino acid antagonists induce a phencyclidine-like catalepsy in pigeons: Structure-activity studies

The excitatory amino acid antagonists -2-amino-5-phosphonovalerate (-AP5), its isomers -(-)-AP5 and -(+)-AP5, -2-amino-4-phosphonobutyrate (AP4), -2-amino-7-phosphonoheptanoate (AP7), [beta]--aspartylaminomethylphosphonic acid (ASP-AMP), cis-2,3-piperidinedi-carboxylic acid (cis-PDA), and [gamma]--glutamylaminomethylsulphonic acid (GAMS) were tested for their ability to produce a phencyclidine (PCP)-like catalepsy in pigeons when administered intracerebro-ventricularly. Each of the antagonists produced catalepsy, although -AP5, and the non-selective antagonists GAMS and cis-PDA, produced the effect only at toxic doses. The rank order of potency to produce catalepsy was AP7 > -AP5 > -AP5 > cis-pda > ASP-AMP > AP4 > -AP5 > GAMS; there was a strong positive correlation between this rank order of potency vivo and the potency order of these compounds in vitro as NMDA antagonists. The antagonists did not displace significant amounts of [3H]N[1-(2-thienyl)cyclohexyl]piperidine (a congener of phencyclidine) from its recognition site in the brain of pigeon. Thus, the PCP-like catalepsy that is produced by the excitatory neurotransmission at NMDA-preferring receptors that are distinct from, but related to, PCP receptors. The results strongly support the hypothesis that a reduction of neurotransmission at excitatory synapses, utilizing NMDA-preferring receptors, may underlie catalepsy in pigeons induced by PCP.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26604/1/0000145.pd

Ontogeny of NET expression and antidepressant-like response to desipramine in wild-type and SERT mutant mice

Abstract word count: 250 Introduction word count: 74

Phencyclidine-induced catalepsy in pigeons: Specificity and stereoselectivity

A procedure is described for the rapid assessment of cataleptic activity (loss of righting, without head-drop and without eye closure) of phencyclidine-type drugs. Single- and cumulative-dosing procedures with phencyclidine and ketamine produced similar results. Pentobarbital produced loss of righting at doses which also induced head-drop and eye closure. Catalepsy was induced exclusively by the d-isomers of ketamine, 1-(1-phenylcyclohexyl)-3-methylpiperidine and [alpha]-dioxadrol. The procedure is suitable for studying compounds which may interact with phencyclidine receptors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24637/1/0000048.pd