Time-dependent changes in brain monoamine oxidase activity and in brain levels of monoamines and amino acids following acute administration of the antidepressant/antipanic drug phenelzine.

Phenelzine (PLZ) is a non-selective monoamine oxidase (MAO) inhibitor commonly used to treat depression and panic disorder. Acute administration of PLZ produces several neurochemical changes, including an increase in brain levels of the catecholamines norepinephrine (NE) and dopamine (DA), of 5-hydroxytryptamine (5-HT), and of the amino acids alanine and gamma-aminobutyric acid (GABA). The goal of the present series of experiments was to characterize the time course of these PLZ-induced changes. Male Sprague-Dawley rats were sacrificed 6, 24, 48, 96, 168, or 336 hr after acute PLZ administration (15 or 30 mg/kg, i.p., based on free base weight). Whole brain levels of monoamines and amino acids were determined using HPLC, and MAO A and B activities were determined using a radiochemical procedure. The results indicated that PLZ changed amino acid levels 6 and 24 hr after injection, but not 48 hr later. In contrast, the effects of PLZ on MAO activity and monoamines were longer-lasting. For example, PLZ-induced increases in dopamine and 5-HT were observed 1 week after injection, and PLZ-induced inhibition of MAO activity persisted for 2 weeks. Thus, in addition to demonstrating that the effects of PLZ on MAO activity and monoamines were long-lasting, these results indicate that the effects of PLZ on MAO activity and on brain levels of monoamines and amino acids are temporally dissociated. These findings regarding the long-term effects of PLZ on neurochemistry will have considerable critical implications for the design and interpretation of behavioral studies of the acute effects of PLZ.

Task-dependent effects of the antidepressant/antipanic drug phenelzine on memory.

Phenelzine (PLZ) is a non-selective monoamine oxidase (MAO) inhibitor commonly used to treat depression and panic disorder. In addition to increasing levels of biogenic amines in the brain, PLZ elevates brain levels of the amino acid gamma-aminobutyric acid (GABA; Baker et al. 1991; present study). Given the extensive evidence implicating biogenic amines and GABA in mnemonic processes, PLZ may affect learning and memory. To investigate this possibility, male Sprague-Dawley rats were given PLZ sulfate (15 or 30 mg/kg, based on free base weight) 2 h prior to training in a continuous multiple trial inhibitory avoidance (CMIA) and spatial water maze task. Retention was assessed 48 h later. The results indicated that PLZ enhanced CMIA and impaired water maze retention performance. Compared to control rats, rats given PLZ took significantly longer to re-enter the shock compartment and swam longer distances before reaching the escape platform on the retention tests. These effects of PLZ did not appear to be the result of PLZ-induced changes in acquisition or retrieval processes, activity levels, or footshock sensitivity. Combined, these findings indicate that PLZ influences memory in a task-dependent manner. These differential effects of PLZ may be the result of contrasting influences of GABA and biogenic amines on memory.

Optoelectronic Recoded and Nonrecoded Trinary Signed-Digit Adder that uses Optical Correlation.

A symbolic-substitution-based optical numeric processor that uses recoded and nonrecoded trinary signed-digit (TSD) number representations is proposed. Also, we propose new joint spatial encodings for the TSD numbers that reduce the symbolic-substitution computation rules involved in the processor. Optoelectronic implementation of the proposed recoded adder is feasible. Also, the nonrecoded TSD addition can be performed optically in two steps. Both the proposed recoded and nonrecoded adders are more compact than a recently reported modified signed-digit counterpart and use fewer correlators and spatial light modulators.

Neuron type processor modeling using a timed Petri net.

The basic operation of a digital neuron is reviewed, and the theory of time Petri nets used for modeling, representation, and analysis of the neuron-type processor (NTP) is reviewed. The timed Petri net is utilized to produce a model for the digital NTP. The neuron-type processor performs input temporal and spatial summation, as well as thresholding. The timed Petri net of the NTP operates asynchronously and sequentially takes on a series of distinct internal states, so that each of these states can concurrently realize a distinct set of steering switching functions depending on the pattern of steering inputs applied to it at the time. This model is structured using several subnets, called essential module units. Depending on the desired number of input dendrites required for the NTP, the essential module units (EMU) are interconnected to produce the required timed Petri net. The timed Petri net and representation facilitates a method of analysis of neural net works containing NTPs prior to hardware implementation.

Dynamics of neuronal firing correlation: modulation of "effective connectivity".

1. We reexamine the possibilities for analyzing and interpreting the time course of correlation in spike trains simultaneously and separably recorded from two neurons. 2. We develop procedures to quantify and properly normalize the classical joint peristimulus time scatter diagram. These allow separation of the "raw" correlation into components caused by direct stimulus modulations of the single-neuron firing rates and those caused by various types of interaction between the two neurons. 3. A newly developed significance test ("surprise") is applied to evaluate such inferences. 4. Application of the new procedures to simulated spike trains allowed the recovery of the known circuitry. In particular, it proved possible to recover fast stimulus-locked modulations of "effective connectivity," even if they were masked by strong direct stimulus modulations of individual firing rates. These procedures thus present a clearly superior alternative to the commonly used "shift predictor." 5. Adopting a model-based approach, we generalize the classical measures for quantifying a direct interneuronal connection ("efficacy" and "contribution") to include possible stimulus-locked time variations. 6. Application of the new procedures to real spike trains from several different preparations showed that fast stimulus-locked modulations of "effective connectivity" also occur for real neurons.