Biomedical subjects

Clinton D Kilts

Publications and source records attributed to Clinton D Kilts.

23 records · Page 2Linked to original sources

PubMed2003

Potential new drug delivery systems for antidepressants: an overview.

Oral administration is probably a nonoptimal delivery system for most psychotropics. Scientists are turning to optimizing drug delivery as a method for enhancing antidepressant response. Advances in oral drug delivery have come in the form of sustained-release formulations of antidepressants, which have smoothed the plasma drug concentration maxima and minima, thus decreasing side effects and increasing tolerability. The future of pharmacologic treatment for psychiatric disorders may be in part dependent on nonoral drug delivery systems such as implantable and transdermal delivery systems. Like the available sustained-release formulations of antidepressants, these alternative delivery systems will have enhanced safety, tolerability, and efficacy because of their ability to maintain a more constant circulating drug level. Implantable devices that sense, stimulate, deliver to, and record from biological systems are being developed through microtechnology and nanotechnology. Transdermal delivery techniques, such as passive diffusion, sonophoresis, electroporation, and iontophoresis, enhance the skin's permeability to drugs. Iontophoresis appears to be a promising and perhaps the most efficient assisted-delivery technique for future antidepressant transdermal delivery.

Administration, Oral↗

PubMed2002

Measurement of dopamine transporter occupancy for multiple injections of cocaine using a single injection of [F-18]FECNT.

The fraction of transporters occupied following injection of specific inhibitors is an important parameter for defining and comparing the molecular mechanisms of different drugs. This work generalizes the reference tissue method to estimate dopamine transporter occupancy for two levels of cocaine administration using only a single injection of [(18)F]FECNT. The results are validated by comparison with literature values. Five rhesus monkeys were studied. On each animal, a baseline scan was collected following [(18)F]FECNT injection (phase a). At 120 min postinjection, 0.1 mg/kg cocaine was injected and the animal was scanned for 50 additional min (phase b). Then 1.0 mg/kg cocaine was injected and another 50-min scan sequence was collected (phase c). Time-activity curves (encompassing all three phases) were generated for each animal from regions drawn over the putamen and cerebellum. The putamen curve was modeled using the cerebellum as the input function. Percent DAT occupancy following the cocaine injections was determined by comparing k(3)/k(4) = B(max)/k(D) for the three phases. The 0.1 and 1.0 mg/kg cocaine doses occupied 53% +/- 5% and 87% +/- 5% of the transporters, respectively. The measured occupancies are consistent with literature values that maintain self-administration in animals and produce a "high" in human subjects. This work demonstrates that a single injection of [(18)F]FECNT can be used to measure the effects of multiple cocaine challenges. Two advantages of this technique are: reduced variability in dose-response curves because the subject is his/her own control, and the (18)F label allows evaluation of longer-acting drugs.

Algorithms↗

PubMed2002

Effects of neurotensin receptor antagonism on latent inhibition in Sprague-Dawley rats.

RATIONALE: It has been postulated that the tridecapeptide neurotensin (NT) functions as an endogenous antipsychotic peptide. A critical test of this hypothesis would be to determine if NT is involved in the expression of latent inhibition (LI), a psychophysiological and pharmacological model of schizophrenia. OBJECTIVE: This report describes the effects of disrupting NT neurotransmission by systemic administration of the NT receptor antagonists SR48692 and SR142948A on the acquisition of LI in rats. METHODS: The effects of 30-300 microg/kg SR48692 or 0.1-100 microg/kg SR142948A on the expression of LI following 0, 20 or 30 pre-exposures were first investigated. This was followed by the assessment of the effects of 10 microg/kg SR142948 A on the LI effect of increasing stimulus pre-exposures (10-40). Finally, the role of dopamine transmission in the effects of SR142948A on the acquisition of LI (30 pre-exposures) was tested by coadministering 10 microg/kg SR142948A and 100 mg/kg of the dopamine D(2) antagonist sulpiride. RESULTS: The higher tested doses of SR48692 (100-300 microg/kg) and SR142948A (10-100 microg/kg) decreased acquisition of LI following 20, 30 and even 40 pre-exposures to the to-be-conditioned stimulus. Cotreatment with the dopamine D(2) antagonist sulpiride prevented the LI-disrupting effects of SR142948A. CONCLUSIONS: NT neurotransmission appears to be necessary for the acquisition of LI. The main effect of NT receptor antagonism is a disruption of LI, most likely via enhancement of dopamine transmission. This effect is opposite that of antipsychotic drugs, which have been shown to enhance NT release, supporting the hypothesis of NT as an endogenous antipsychotic peptide.

Adamantane↗

PubMed2002

Ecstasy and agony: activation of the human amygdala in positive and negative emotion.

Considerable evidence indicates that the amygdala plays a critical role in negative, aversive human emotions. Although researchers have speculated that the amygdala plays a role in positive emotion, little relevant evidence exists. We examined the neural correlates of positive and negative emotion using positron emission tomography (PET), focusing on the amygdala. Participants viewed positive and negative photographs, as well as interesting and uninteresting neutral photographs, during PET scanning. The left amygdala and ventromedial prefrontal cortex were activated during positive emotion, and bilateral amygdala activation occurred during negative emotion. High-interest, unusual photographs also elicited left-amygdala activation, a finding consistent with suggestions that the amygdala is involved in vigilance reactions to associatively ambiguous stimuli. The current results constitute the first neuroimaging evidence for a role of the amygdala in positive emotional reactions elicited by visual stimuli. Although the amygdala appears to play a more extensive role in negative emotion, it is involved in positive emotion as well.

Adult↗

PubMed1987

CSF monoamine metabolites in chronic pain.

Metabolites of selected neurotransmitters (5-HIAA, HVA and DOPAC) and beta-endorphin were measured in the CSF of 39 chronic pain patients and compared to controls. Twelve of the pain patients also fulfilled criteria for major depression. The concentration of 5-HIAA was increased in female but not male pain patients; there was no significant difference in the CSF concentrations of HVA and DOPAC. The presence of depression did not influence the concentrations of neurotransmitters. No correlation was found between the concentrations of monoamine metabolites and beta-endorphin. However, there was a positive correlation between 5-HIAA and HVA in controls and chronic pain patients without depression but not in depressed patients. It is concluded: chronic pain states are associated with elevation of CSF 5-HIAA in female patients; depression abolishes a positive correlation between 5-HIAA and HVA.

3,4-Dihydroxyphenylacetic Acid↗