Edna Cohen

Cytokines, “Depression Due to A General Medical Condition,” and Antidepressant Drugs

Activation of the immune system during various medical conditions produces neural, neuroendocrine, and behavioral effects. The psychological and physiological effects of immune activation resemble many characteristics of depression. The essential features of depression are depressed mood and loss of interest or pleasure in all, or almost all activities (anhedonia). Several associated symptoms are also present, including, appetite disturbance, change in body weight, sleep disturbance, psychomotor disturbance, fatigue, loss of energy, and difficulty in thinking or concentrating (DSM-IV, 1994). Depression is also characterized by specific alterations in the functioning of neurochemical and neuroendocrine systems, including monoaminergic systems and the hypothalamic-pituitary-adrenal (HPA) axis (Brown, Steinberg, & van Praag, 1994; Holsboer, 1995). Most of these psychological and neuroendocrine symptoms appear both in humans and animals during diseases that involve immune activation. Based on these findings, and on several additional lines of evidence that will be presented below, we have recently argued that immune activation is involved in the etiology and symptomatology of depression associated with various medical conditions (Yirmiya, 1997).

Prevention of soman-induced cognitive deficits by pretreatment with human butyrylcholinesterase in rats

This study examined the ability of pretreatment with human serum butyrylcholinesterase (HuBChE) to prevent soman-induced cognitive impairments. Behavioral testing was carried out using the Morris water maze task evaluating learning, memory, and reversal learning processes. Pretreatment with HuBChE significantly prevented the memory and reversal learning impairments induced by soman. A small deficiency in performance was observed only during part of the learning period in HuBChE-treated rats after administration of soman. Results support the contention that pretreatment alone with HuBChE is sufficient to increase survival and to prevent impairment in cognitive functioning following exposure to soman.

Influence of intake of sweet solutions on the analgesic effect of a low dose of morphine in randomly bred rats

The time course for the development of morphine tolerance, following prolonged sweet intake, was examined in randomly bred Sabra rats. Exposure to 3% glucose in 6 mM saccharin solution increased drinking by about three times as compared to rats supplied only with water. Suppression of the analgesic effect of morphine was already detectable after 24 h of intake and became progressively more marked within the next 5 weeks. These results support an active interaction between sweet consumption and endogenous opioids in randomly bred rats.

Effects of Interleukin-1 on Sexual Attractivity in a Model of Sickness Behavior

Interleukin-1 (IL-1), a cytokine secreted by activated macrophages, inhibits sexual behavior in female but not male rats. The present study examined the effects of IL-1 on sexual attractiveness of the injected animal and on the sexual responses exhibited by its mating partner. In Experiment 1, a male rat was placed with an estrous female, injected with either IL-1 beta (2 or 10 micrograms/kg) or saline. Males exhibited more mounts and intromissions per ejaculation and longer ejaculation latencies with IL-1- than with saline-injected females. In a second experiment, a male was placed with two estrous females, one injected with IL-1 beta (5 micrograms/kg) and the other with saline. Males performed less sexual behavior and spent less time with the IL-1-injected female. In a third experiment, an estrous female was placed with two males, one injected with IL-1 beta (5 or 20 micrograms/kg) and the other with saline. IL-1 had no effect on the time spent by the female with each male, and only the high dose reduced proceptive (courtship) behavior. In conclusion, IL-1 administration to females reduces the quality of the sexual act, thus reducing the chances for conception during infection, which is associated with spontaneous abortion and abnormal development of the fetus. In males, the chances for reproduction are less affected by IL-1, possibly because reproduction during infection is not as risky in males as in females.

Prenatal morphine enhances morphine-conditioned place preference in adult rats.

Conditioned place preference (CPP) is a commonly used method for assessing the rewarding qualities of drugs, including opiates. In the present study, we examined long-term effects of prenatal morphine on morphine-associated place preference. Pregnant Fischer 344 rats were given increasing doses of morphine (0.75-12.0 mg/day) in slow-release emulsion during gestational days 12-18. Control rats were injected with vehicle and were fed either with morphine rats or ad libitum. At birth, all litters were culled to 8 pups and fostered to naive dams. Testing began when rats were 10-12 weeks old. Rats prenatally exposed to morphine exhibited a significantly higher preference for the morphine-paired compartment, suggesting that prenatal morphine induces a long-lasting enhancement of its reinforcing effect. Thus, prenatal morphine may result in enhanced activity and/or sensitivity of the endogenous opiate system, thereby placing the organism at higher risk for opiate drug abuse.

Effects of capture procedures on emotionality scores in rats with septal lesions.

Abstract Septal-lesioned rats, when approached from below (Anterior-Ventral capture) rather than from above, displayed a remarkably reduced emotionality-score as measured by standard scales. Vocalization and biting were almost completely absent, resistance to capture and handling were considerably reduced; head jerk and vibrissae stiffening were only slightly affected. It is suggested that the septum might be involved in higher order processing of information and that the increased emotionality observed after septal lesioning results from a distorted evaluation of the threat value of sensory input.

Consummatory responses to taste stimuli in rats selected for high and low rates of self-stimulation

Abstract The factors mediating self-stimulation are often considered to coincide with those initiating and maintaining avid intake of sweet-tasting substances. The availability of two populations of albino rats (LC1 and LC2), each genetically selected for high- and low-self-stimulators, provided an opportunity to test this hypothesis. Consummatory responses of these 4 lines were investigated using a 24-hr two-bottle test. Seven concentrations of sodium saccharin, as well as 8 concentrations of quinine hydrochloride, were each presented against water in a double-blind setting. Lateral hypothalamic self-stimulation rates were then determined. It was found that the population (LC2) exhibiting the largest separation of high and low self-stimulation rates, also was separated most by saccharin solution intakes: The genetically high ICSS responders consumed the most—while the genetically low ICSS responders of that population drank the least—saccharin solution across concentrations. In contrast, the effect of genetic line on quinine intake was minimal. Sex was a relevant variable with the females consuming relatively more saccharin solution and bar pressing at higher rates for self-stimulation, than males in each population. On the other hand, there was a tendency for the females of each line to be less rejecting of quinine solutions than males.

Amphetamine-induced stereotypic responses in Roman high- and Roman low-avoidance rats ☆

The effects of 0, 1, 3 and 5 mg/kg d, 1-amphetamine (AMPH) on male RHA/Verh and RLA/Verh rats were measured, at 25 and 55 min post-injection, using an observational method in which six categories of behavior were scored. RHA/Verh rats displayed a more rapid increase of AMPH-induced stereotyped behavior, mostly due to drug-related differences in scanning (head-bobbing), whereas the differences in rearing seen (RHA/Verh greater than RLA/Verh) were attributable to purely genetic effects. These results were compared with those of previous experiments which measured apomorphine-induced stereotyped behavior in these, and other, Roman lines. It was concluded that the RHA/Verh rats probably showed a stronger response to AMPH due to their higher, and more drug-responsive, striatal dopamine turnover rate.

Prenatal exposure to morphine alters analgesic responses and preference for sweet solutions in adult rats

In the present study, we examined long-term effects of prenatal morphine on pain response and on preference for sweet solutions. Pregnant Fischer 344 rats were given increasing doses of morphine (0.75-12.0 mg/day) in slow-release emulsion, during gestational days 12-18. Control rats were injected with vehicle and were either pair-fed to morphine rats, or ad libitum fed. At birth, all litters were culled to 8-10 pups (half males and half females) and cross-fostered to naive, surrogate dams. Testing began when rats were 10-12 week old. Rats prenatally exposed to morphine exhibited higher analgesia in response to a morphine challenge, and a greater preference for saccharin solution as compared with both control groups. These findings indicate that prenatal morphine induces long-lasting alterations of systems involved in reward processes and in opiate analgesia, perhaps by modulating endogenous opiate systems.

Biphasic effects of chronic saccharin intake on pain responses of healthy and diabetic rats of two genetically selected strains

Rats of the LC-2-HI strain, selected for high rates of self-stimulation, were supplied with a 3 mM saccharin solution. Within 1 week they developed markedly prolonged latencies to painful stimuli on a hot-plate. In contrast, a similar effect became manifest in LC-2-LO rats only after 3 weeks. Both strains of rats were made diabetic by injection of streptozotocin. LO rats showed more polydipsia and hyperglycemia than HI rats and, when drinking saccharin solution, developed cross-tolerance to morphine within about 2 weeks. It is assumed that saccharin consumption stimulates the release of endogenous opioid peptides, probably via stimulation of gustatory sweet receptors. The opioid peptides exert a biphasic effect: initially they raise the pain threshold, but at a later stage they cause chronic crosstolerance to morphine.