Apomorphine-induced hypothermia increases during ethanol withdrawal.

Changes in several measures of dopamine function have been observed following acute or chronic ethanol exposure. The present study examined the effects of chronic ethanol exposure on the hypothermia following acute administration of the dopamine agonist apomorphine. Animals withdrawn from chronic ethanol exposure showed a significantly greater decrease in body temperature following apomorphine than did ethanol-naive controls, suggesting an increase in sensitivity to dopaminergic stimulation during ethanol withdrawal.

Some characteristics of TRH-induced grooming behavior in rats.

Intracerebroventricular administration of TRH induces excessive grooming behavior that is characterized by an important contribution of the elements scratching and paw licking. As compared with other grooming inducing peptides, the pattern of TRH-induced grooming resembles that induced by beta-endorphin rather than those elicited by ACTH or bombesin. TRH-induced excessive grooming is suppressed by pretreatment with haloperidol, naloxone or neurotensin. Haloperidol suppresses TRH-induced grooming in a general way, whereas the suppressive effect of the other drugs is mainly due to a selective reduction of TRH-induced excessive scratching. Combined treatments of rats with TRH and a submaximal dose of ACTH, bombesin or beta-endorphin do not result in higher grooming scores than with single peptide treatment. Excessive grooming elicited by water immersion is not affected by TRH. It is concluded that TRH is undoubtedly an excessive grooming inducing peptide. In situations where excessive grooming is elicited by other peptides or by water immersion, TRH does not further activate the operating systems involved in the existing excessive grooming.

Molecular transduction mechanisms in ACTH-induced grooming.

Intraventricular administration of ACTH1-24 induces excessive grooming in the rat. Ethogram analysis shows that the peptide does not alter grooming behavior seen in a novel box, but that it prolongs the duration of the grooming bout. Extensive structure-activity studies have been performed which suggest that the active site lies in a region (5-13) of the ACTH molecule. Interestingly, the (1-24) sequence is fully active, whereas (1-10) and (11-24) alone or in combination are inactive, pointing to a specific stereoconformation necessary to induce grooming. However, despite the fact that there are ACTH-and/or alpha-MSH-containing peptidergic neurons, no conclusive evidence is available demonstrating stereospecific, saturable binding sites for these peptides in brain. The analysis of the neural substrate underlying ACTH-induced excessive grooming has been performed by means of electrolytic lesions of specific brain regions and by neuropharmacological manipulations. The data suggest that the periaqueductal gray is the primary target for ACTH and that the activity of neostriatum and accumbens, via a nigro-colliculus-periaqueductal gray pathway, modulates the display of excessive grooming. An important feature of the neural substrate is that it displays single-dose tolerance to the peptide during the first hours after the first peptide injection. It is suggested that the tolerance is a feature of an opioid receptor-containing component of the neural substrate. The molecular mechanism of action of ACTH is complex and may involve different transmembrane signal transduction systems. The peptide decreases the degree of phosphorylation of a neuron-specific, synaptic phosphoprotein B-50 by inhibition of protein kinase C. It is concluded that changes in the degree of phosphorylation of B-50 regulate the activity of the lipid kinase phosphatidylinositol 4-phosphate kinase. Therefore, the B-50 protein seems to be part of a negative feedback loop in the receptor-activated hydrolysis of phosphatidylinositol 4,5-bis-phosphate (PIP2). There is increasing evidence that the molecular mechanism by which ACTH brings about the grooming response involves a change in phosphorylation of B-50. Firstly, the structure-activity relationship of ACTH-induced excessive grooming is nearly identical to that obtained for ACTH-induced inhibition of protein kinase C.(ABSTRACT TRUNCATED AT 400 WORDS)

The influence of neurotensin, naloxone, and haloperidol on elements of excessive grooming behavior induced by ACTH.

Naloxone, haloperidol, and neurotensin suppress ACTH-induced grooming. The suppressive effects of naloxone and of haloperidol on ACTH-induced grooming are observed following subcutaneous as well as intracerebroventricular administration. The suppression of ACTH-induced grooming by these drugs is not accompanied by a change in the relative distribution of grooming elements. From previous data and from the results of the present study it is suggested that the underlying substrate involved in ACTH-induced excessive grooming may differ from that of bombesin-induced grooming.

The effect of home or novel environment on the facilitation of passive avoidance by post-training ethanol.

Passive avoidance behavior of mice is improved when mice are injected with ethanol immediately after footshock training. Further study has shown that avoidance can be affected by ethanol injections given within 1 h, but not at 90 or 180 min, after training. The present study was conducted to investigate the possibility that events which occur in the homecage during this sensitive period may influence the effect of ethanol on subsequent avoidance. Male Swiss-Webster mice were housed either singly in a novel environment for 90 min or returned to their (group) homecage following one-trial, step-through, passive avoidance training (0.1 mA footshock) and intraperitoneal injection of 3.0 g/kg ethanol (15% v/v) or saline. As in previous studies, when ethanol-treated mice were returned to their homecage, avoidance was significantly increased at 24 h compared to the behavior of saline-treated mice. However, when mice were isolated in the novel environment for 90 min immediately following treatment, the memory facilitating effects of ethanol were not observed. The avoidance behavior of mice injected with saline was the same regardless of their post-training environment. Also, the number of mice (6 or 10) housed per homecage did not significantly influence the effects of ethanol or post-training environment on avoidance. These findings indicate that environmental factors may interact with the effects of ethanol to modify avoidance behavior. The possible influence of variables such as aggression, thermoregulation, and behavioral arousal on the effects of ethanol in this paradigm are discussed.

The effects of neurotensin, naloxone and haloperidol on elements of excessive grooming behavior induced by bombesin.

The influence of naloxone, haloperidol and neurotensin was investigated on bombesin-induced excessive grooming in rats. All three drugs reduced the amount of bombesin-induced grooming. Haloperidol induced a general reduction in excessive grooming as induced by bombesin, without changing the composition of grooming behavior, whereas naloxone and neurotensin suppressed bombesin-induced grooming and caused a shift in the distribution of grooming elements. The main suppressive effect of these latter drugs appeared to be on the element scratching. From these data it is suggested that bombesin-induced scratching is mainly displayed by activation of opiate receptor systems, whereas the other elements of bombesin-induced excessive grooming are mainly regulated by dopaminergic systems.

Ethanol increases plasma vasopressin shortly after intraperitoneal injection in rats.

In rats, ethanol has generally been thought to inhibit vasopressin (VP) release into the peripheral circulation; however, the primary evidence for this conclusion has been indirect. Radioimmunoassay was used to measure VP in the plasma of rats decapitated 5 or 60 min after intraperitoneal injection of ethanol (2.0 g/kg). Confirming the popular notion that ethanol inhibits VP release, VP levels were decreased 60 min after treatment. But radioimmunoassay techniques also revealed that VP release is markedly stimulated shortly after an injection of ethanol.

Neurotensin diminishes grooming and stimulates paper shredding behavior induced by water immersion of rats.

Intracerebroventricular (i.c.v.) administration of 2 micrograms neurotensin, a brain and gastro-intestinal peptide which elicits various behavioral responses, diminishes grooming but stimulates paper shredding behavior of rats evoked by water immersion. Neither naloxone (2 micrograms i.c.v.) nor haloperidol (2 micrograms i.c.v.) affect grooming and paper shredding behavior as observed following water immersion of rats.