Rats selectively-bred for behavior related to affective disorders: proclivity for intake of alcohol and drugs of abuse, and measures of brain monoamines.

Several lines of rats potentially useful for studying affective disorders have been developed in our laboratory though selective breeding for behavioral characteristics. The propensity of these lines to consume alcohol and other drugs of abuse (amphetamine and cocaine) was examined. Also, measurement of the concentration of brain monoamines - norepinephrine, dopamine, and serotonin - as well as estimation of their metabolism by measurement of the major extracellular metabolites of these monoamines was carried out to examine possible relationships of brain chemistry to the behavioral characteristics shown by these lines, as well as to their propensity for drug usage. The lines of rats are: Swim Low-active (SwLo) and Swim High-active (SwHi), which show either very low (SwLo) or very high (SwHi) amounts of motor activity in a swim test; Swim-test Susceptible (Susceptible or SUS) and Swim-test Resistant (Resistant or RES), which are highly susceptible (SUS) or highly resistant (RES) to having their swim-test activity depressed by being exposed to a stressful condition prior to the swim test; and Hyperactive (HYPER), which show spontaneous nocturnal hyperactivity compared to non-selectively bred (i.e., normal) rats as well as both extreme hyperactivity and behavioral depression after being exposed to a stressful condition. Regarding alcohol and drug usage, SUS rats readily consume alcohol while all other lines including non-selected, normal rats do not, and SwLo rats show a strong tendency to consume amphetamine and cocaine. Marked differences in brain monoamines were found between the various lines and normal rats, with salient differences seen in norepinephrine, particularly in the hippocampus, and in dopamine in forebrain regions (striatum and nucleus accumbens).

Rats selectively bred for high and low swim-test activity show differential responses to dopaminergic drugs.

RATIONALE: Selective breeding of Sprague-Dawley rats has been used to generate a line of animals with very low swim-test activity (SwLo) in an attempt to model certain characteristics of depression. For comparison with the SwLo animals, a line bred for high swim-test activity (SwHi) and a non-selectively bred line (SwNS) have been generated. Previous studies using these lines suggested an inverse relationship between dopamine (DA) function in the brain and inactivity in the swim test. OBJECTIVES: The current experiments investigated the possibility that SwLo and SwHi rats show differences in central DA processes, as suggested by responsiveness to DA agonists. RESULTS: The increase in ambulation produced by d-amphetamine (0.25-1.0 mg/kg) was largest in SwHi rats and smallest in SwLo rats, with SwNS rats showing an intermediate response. Amphetamine levels in plasma and brain tissue were similar in SwHi and SwLo rats, indicating that pharmacokinetic differences were not responsible for the behavioral differences. Repeated amphetamine administration produced enhancement in the ambulation-increasing effects of this drug (i.e., sensitization), with significant enhancement seen in all three lines. Apomorphine in doses that stimulate postsynaptic receptors (0.25-4.0 mg/kg) produced mainly increased sniffing behaviors in SwHi and SwNS rats and oral behaviors in SwLo rats, suggesting that the lines differ in proportions of D1, D2, and D3 postsynaptic receptors. CONCLUSIONS: The findings suggest that DA function differs in lines of rats selectively bred for differences in swim behavior, a feature that may make these lines useful for studying certain depressive symptoms that might be related to DA function.

Galanin: a significant role in depression?

This paper describes a hypothesis that attempts to account for how changes in noradrenergic systems in the brain can affect depression-related behaviors and symptoms. It is hypothesized that increased activity of the locus coeruleus (LC) neurons, the principal norepinephrine (NE)-containing cells in the brain, causes release of galanin (GAL) in the ventral tegmentum (VTA) from LC axon terminals in which GAL is colocalized with NE. It is proposed that GAL release in VTA inhibits the activity of dopaminergic cell bodies in this region whose axons project to forebrain, thereby resulting in two of the principal symptoms seen in depression, decreased motor activation and decreased appreciation of pleasurable stimuli (anhedonia). The genesis of this hypothesis, which derives from studies using an animal model of depression, is described as well as recent data consistent with the hypothesis. The formulation proposed suggests that GAL antagonists may be of therapeutic benefit in the treatment of depression.

Depletion of brain norepinephrine does not reduce spontaneous ambulatory activity of rats in the home cage.

6-Hydroxydopamine (6-OHDA) lesions of brain noradrenergic neurons and terminals were made in rats to assess the importance of forebrain norepinephrine (NE) for mediating circadian patterns of spontaneous ambulatory activity that rats show in the home cage. 6-OHDA was injected intracranially into the fibers of the ascending noradrenergic dorsal and ventral bundle pathways or infused into the lateral ventricle or both. Rats living in a 12/12 h light/dark cycle exhibit a marked increase in ambulatory activity during the dark period in comparison to the light period and a 'W-shaped' pattern of activity during the 12 h of the dark phase. Results showed that near-total depletion of brain NE did not impair the capacity to generate normal patterns of spontaneous ambulatory activity that occur in the home cage. In the animals that sustained the most complete NE lesions, the amounts of activity generated at times of peak activity were exaggerated in comparison to the control animals, which is consistent with the possibility that NE in the brain exerts a moderating influence on behavior.

The effect of lower-extremity position on cerebrospinal fluid pressures.

OBJECTIVE: To determine the effects of lower-extremity positioning on cerebrospinal fluid opening pressure (CSFp). The authors believed that during lumbar puncture (LP), CSFp does not meaningfully decrease when the lower extremities are extended from flexion, as is often suggested. METHODS: In a convenience sample of adult patients who clinically required LP in an urban emergency department, three sequential CSFp measurements were obtained in either sequence A (knee, hip, and neck flexion [90 degrees ], then extension, then flexion) or sequence B (extension, flexion, then extension) prior to CSF withdrawal. The neck was flexed at 30 degrees when the lower extremities were flexed, while the thoracolumbar spine was kept in the neutral position for all measurements. RESULTS: Nineteen patients were studied in each sequence. Although variable, overall within-patient changes between positions were not clinically meaningful. Mean and 95% confidence intervals (95% CIs) for the decrease in CSFp from position 1 to position 3 (same position) were 0.2 cm H(2)O (1.7%) and 0.9 to -0.6 cm H(2)O (6% to -2.7%), respectively. Changing from flexion to extension decreased pressure measurements by a mean of 0.9 cm H(2)O (2.5%) [95% CI = 2.1 to -0.1 cm H(2)O (7.6% to -2.4%)]. Changing from extension to flexion increased CSFp by a mean of 1.1 cm H(2)O (6.1%) [95% CI = 0.2 to 2.0 cm H(2)O (1.3% to 11.5%)], a statistically but not clinically meaningful change. CONCLUSIONS: Changing lower-extremity position did not meaningfully change mean CSFp. These data do not support the common suggestion that extending the lower extremities during LP meaningfully decreases CSF opening pressures.

Coherent imaging with two-dimensional focal-plane arrays: design and applications.

Scanned, single-channel optical heterodyne detection has been used in a variety of lidar applications from ranging and velocity measurements to differential absorption spectroscopy. We describe the design of a coherent camera system that is based on a two-dimensional staring array of heterodyne receivers for coherent imaging applications. Experimental results with a single HgCdTe detector translated in the image plane to form a synthetic two-dimensional array demonstrate the ability to obtain passive heterodyne images of chemical vapor plumes that are invisible to normal video infrared cameras. We describe active heterodyne imaging experiments with use of focal-plane arrays that yield hard-body Doppler lidar images and also demonstrate spatial averaging to reduce speckle effects in static coherent images.

Telesensor integrated circuits.

Progress in personal computing has recently permitted small research programs to design and simulate application-specific integrated circuits (ASICs). Inexpensive fabrication of silicon chips can then be obtained using chip foundries, and quite complex circuits can be greatly reduced in size with an accompanying increase in certain performance characteristics. Within the past 5 years it has also become possible to design ASICs which can transmit and receive radio signals and which thus may be employed in applications in which wired connections for input and output of signals are not practicable. We are currently developing research-grade prototype ASICs for the monitoring of human vital signs. In this case one or more sensors placed on an ASIC provides a signal to be transmitted a distance of 2-3 meters to a receiver/display unit. The use of ASIC telesensors provides the possibility of wireless monitoring, including long-term monitoring, with inexpensive and unencumbering devices. Their self-contained nature permits a number of potential uses in future biomedical applications as new sensors are devised which are amenable to deployment on silicon.