Biomedical subjects

J Pierri

Publications and source records attributed to J Pierri.

6 recordsLinked to original sources

PubMed2001

GABA transporter-1 mRNA in the prefrontal cortex in schizophrenia: decreased expression in a subset of neurons.

OBJECTIVE: Within the prefrontal cortex of schizophrenic subjects, alterations in markers of gamma-aminobutyric acid (GABA) neurotransmission, including decreased immunoreactivity for the GABA membrane transporter GAT-1, may be most prominent in a subset of inhibitory neurons. In the present study, the authors sought to determine whether the alterations in GAT-1 protein could be attributed to a reduction in GAT-1 mRNA expression. METHOD: Tissue sections containing prefrontal cortex area 9 from 10 matched pairs of schizophrenic and comparison subjects were processed for in situ hybridization histochemistry with (35)S-oligonucleotide probes for GAT-1 mRNA. RESULTS: In the schizophrenic subjects, the relative density of labeled neurons was 21%-33% lower in layers 1-5 of the prefrontal cortex but was unchanged in layer 6. In contrast, cellular levels of GAT-1 mRNA expression, as reflected in grain density per labeled neuron, did not differ by more than 11% between subject groups in any layer. These findings indicate that GAT-1 mRNA expression is relatively unaltered in the majority of prefrontal cortex GABA neurons in schizophrenic subjects but is reduced below a detectable level in a subset of GABA neurons. Furthermore, the magnitude and laminar pattern of these results were strikingly similar to those found in a previous study of mRNA expression for the synthesizing enzyme of GABA, glutamic acid decarboxylase(67), in the same subjects. CONCLUSIONS: Both GABA synthesis and reuptake appear to be altered at the level of gene expression in a subset of GABA neurons, and the resulting changes in GABA neurotransmission may contribute to prefrontal cortex dysfunction in schizophrenia.

Adult↗

PubMed1989

Assessing individual differences in ethanol preference using a cumulative dosing procedure.

Preference for ethanol versus a placebo was assessed in 12 normal volunteers usina a cumulative dosing preference test. The test consisted of four sampling sessions followed by three choice sessions. During the sampling sessions subjects received either five cumulating oral doses of ethanol (0.1 g/kg per dose) or equal volumes of placebo, at 15-min intervals. Subjective and observer-rated drug effects, psychomotor performance, drug liking ratings, and breath ethanol levels were measured at regular intervals. During choice sessions, subjects first chose which of the two substances (drug or placebo) they wished to take and ingested one unit dose. Then, at 15-min intervals throughout the session, they could ingest up to ten additional unit doses of the same substance (i.e., up to 1.1 g/kg ethanol). On average, the subjects chose the ethanol-containing beverage on 75% of the choice sessions, and they self-administered a mean total dose of 0.8 g/kg per session. Subjects varied in the amount of ethanol ingested on choice sessions, and the amount they chose was related to their subjective responses to the drug during sampling. Subjects who chose the most ethanol, whereas the subjects who chose ethanol less frequently and ingested lower doses reported primarily sedative-like effects from the drug. The results demonstrate that the cumulative dosing procedure can be used effectively to evaluate drug preferences and dose preferences in normal volunteers.

Adult↗

PubMed1989

Assessing pentobarbital preference in normal volunteers using a cumulative dosing procedure.

Preference for pentobarbital was assessed in 12 normal healthy volunteers using a seven-session cumulative dosing choice procedure. On the first four sessions subjects sampled the drug and a placebo, and on the last three sessions they chose the substance they preferred. During each of the sampling sessions they ingested, at 30-min intervals, five capsules containing either pentobarbital (30 mg per dose) or placebo. During the choice sessions subjects first chose which capsules they preferred to take (drug or placebo), and then took from one to seven of these capsules, separated by 30 min between ingestions. Self-report measures of subjective effects were obtained at regular intervals during each session. Subjects chose the pentobarbital-containing capsules on average 52% of choice sessions, and ingested an average total dose of 132 mg. Although the drug produced only modest, sedative-like subjective and behavioral effects and there was little evidence of euphoric effects in the group as a whole, individual differences in drug liking and choice were observed. The results are discussed in terms of variables that affect the reinforcing effects of pentobarbital in normal volunteers, and they are contrasted to previous findings using this procedure with other sedative drugs.

Adult↗

PubMed1989

Reinforcing and subjective effects of diazepam in nondrug-abusing volunteers.

Preference for diazepam was assessed in 18 light and 12 moderate social drinkers using a cumulative dosing procedure. The 7-session procedure consisted of: 1) four sampling sessions, during which participants ingested color-coded capsules containing either diazepam (five 4-mg capsules administered at 30-min intervals; total dose 20 mg) or placebo, and 2) three choice sessions, during which they could ingest up to 7 capsules of their preferred color of capsule, each separated by 30 min. Subjective (mood) and behavioral (performance) measures were obtained throughout the 4-hour sessions. The light social drinkers chose diazepam over placebo on 66% of the choice sessions, and ingested a mean dose per session of about 16 mg. The moderate drinkers chose diazepam on 100% of the choice sessions, and ingested an average dose of 25 mg per session. Diazepam produced sedation in both groups, but in the moderate drinkers it also increased measures of subjective effects suggestive of "euphoria." The results indicate that diazepam can serve as a positive reinforcer under laboratory conditions in nondrug-abusing individuals who are moderate users of alcohol and other drugs. Greater reinforcing efficacy may be indicative of higher risk of abuse. The results illustrate the usefulness of the cumulative dosing procedure to measure both drug preference and dose preference.

Adult↗

PubMed1989

Some physical characteristics of NIDA marijuana cigarettes.

Marijuana cigarettes of three different potencies (0.0%, 1.4% and 2.7% delta-9-tetrahydrocannabinol (THC) content) provided by the National Institute on Drug Abuse (NIDA) were compared on a variety of characteristics, including physical appearance, weight, burn rate, and deliveries of total particulate matter and carbon monoxide. Significant differences between the different potency cigarettes were obtained on most measures. These differences could be relevant to the design and interpretation of pharmacologic/toxicologic and behavioral studies conducted with these cigarettes. The possible basis for these observed differences, methods for minimizing some of them, and other potential problems related to the use of NIDA marijuana cigarettes are discussed.

Cannabis↗

PubMed1987

Individual differences in behavioral and subjective responses to alcohol.

The reinforcing properties and subjective effects of alcohol were assessed in 29 normal volunteers using a seven-session choice procedure. On the first four sessions, subjects sampled an alcohol (0.5 g/kg) and a placebo beverage twice each. On three subsequent choice sessions, subjects chose the drink they preferred. The number of times they chose alcohol was the measure of its reinforcing properties. On all sessions subjects completed mood questionnaires before and several times after consuming the beverage. Other dependent measures during the experiment included a cognitive performance task, drug liking and identification questionnaires, and breathalyzer alcohol determinations. Demographic and personality data also were obtained. Approximately one-third of the subjects chose the alcohol-containing beverage on all three choice sessions, one-third alternated in their choices of alcohol and placebo, and one-third consistently chose the placebo. When the subjective effects of alcohol (determined during sampling sessions) were compared across the three choice groups, qualitative differences in response to alcohol were observed. For example, alcohol increased elation and vigor scores in the consistent choosers of alcohol, whereas it decreased scores on these measures in the consistent placebo choosers. Consistent alcohol choosers did not differ from placebo choosers in gender or age but they reported more marijuana use and slightly more alcohol use outside the laboratory. They also scored higher on certain measures of arousal and depression, on the Sensation Seeking Scale and on the Psychopathic State Inventory. The results are discussed in terms of individual differences in vulnerability to excessive use of alcohol.

Adult↗