Effects of naltrexone on food preference and concurrent behavioral responses in food-deprived rats.

Naltrexone (0.05-5.0 mg/kg, SC) was administered to food-deprived rats prior to a 15-min food-preference test. Total food intake and feeding duration was reduced following administration of the opiate antagonist. However, while naltrexone reduced the consumption of the initially-preferred chocolate-coated cookies, the ingestion of the nonpreferred standard laboratory chow pellets was significantly enhanced. These data cannot be explained in terms of a general anorexic effect and nonspecific suppression of feeding responses. Instead, they indicate that naltrexone reduced preference for the highly palatable cookies, so that a feeding response to the chow pellets emerged. Under the conditions of test-familiarity, naltrexone did not reduce grooming, locomotion or rearing duration. An increase in locomotion may have been secondary to the reduction in feeding. The results agree with previous data from animal and human studies in suggesting that endogenous opioid peptide activity is involved in the palatability of preferred foods.

Monoamine oxidase-B inhibition: a comparison of in vivo and ex vivo measures of reversible effects.

A behavioural test involving potentiation of the effects of an acute injection of beta-phenylethylamine (10 mg kg-1 i.p.) was used to assess the time-course of type-B MAO inhibition after administration of (--)deprenyl (5 mg kg-1 i.p.) and of MD 240928 (20 mg kg-1 i.p.) respectively. Potentiation of the effects of beta-phenylethylamine was observed 1 h after injection of (-)deprenyl or MD 240928. This effect was still evident 120 h after administration of (-)deprenyl but not 24 h after administration of MD 240928. Comparisons of ex vivo estimates of MAO activity yielded a corresponding time-course for the recovery of this enzyme. The extent of MAO inhibition required for potentiation of the effects of beta-phenylethylamine was inferred from a comparison of the behavioural test results and the ex vivo MAO activity observed after (-)deprenyl administration. These comparisons indicate a significant underestimation of MD 240928-induced MAO inhibition using ex vivo measures. This underestimation is interpreted as evidence for dilution effects in the ex vivo assay of MAO inhibition. The potentiation of effects of beta-phenylethylamine under the present conditions is proposed as a useful and simple test for effects of reversible type-B MAO inhibitors.

Effects of a kappa receptor agonist, ethylketocyclazocine, on water consumption in water-deprived and nondeprived rats in diurnal and nocturnal tests.

In 24 hr water-deprived male hooded rats, ethylketocyclazocine (EKC), 0.1-3.0 mg/kg, dose-dependently suppressed water intake. Within the first 30 min access to water, drinking was virtually abolished by 1.0 and 3.0 mg/kg EKC. Significant reductions in the level of water intake were found after 0.1 mg/kg EKC. After 2 hr access to water, the suppressant effect was attenuated indicating some recovery. The antidipsogenic action of EKC in water-deprived rats was comparable in its effect for both daytime and nocturnal testing. Circadian variation may not be an important modulator of the antidipsogenic action. Naloxone, an opiate receptor antagonist, when administered in a dose of 0.3 mg/kg also significantly reduced drinking in deprived animals. EKC (0.3 mg/kg) and naloxone (0.3 mg/kg) when administered together displayed mutual antagonism. Drinking was at control levels. In nondeprived male rats, EKC exerted some dipsogenic action, most noticeably during diurnal testing. Within 30 min access to water, 0.1 mg/kg EKC significantly elevated the level of water intake. This effect did not occur during nocturnal testing, when the only immediate effect of EKC was a suppression of drinking at 1.0 and 3.0 mg/kg dose levels. After 2 hr access to water, there was a significant peak effect to enhance drinking at the 0.3 mg/kg dose level during the daytime. Effects of EKC during the night were less pronounced. The dipsogenic action of EKC (0.3 and 1.0 mg/kg) in satiated animals during the day was abolished by naloxone and Mr-2266BS, also an opiate receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhancement of saline consumption by chlordiazepoxide in thirsty rats: antagonism by Ro15-1788.

Water-deprived rats were given access to either water or a highly preferred 0.9% NaCl solution in a 30 min drinking test. The animals consumed substantially more saline than water. Chlordiazepoxide (2.5-20.0 mg/kg) was administered IP before the drinking test. Analysis of the results revealed a significant drug treatment X fluid condition interaction. Chlordiazepoxide produced a preferential enhancement of saline intake, achieving a peak effect at 5.0 mg/kg. Consideration of the time-course of drinking showed some complexity in the way in which chlordiazepoxide affected the saline drinking. During the first 6 min of the drinking period, the drug treatments tended to depress consumption, reaching a significant effect at 20.0 mg/kg. However, in the following 16 min interval of the drinking test, chlordiazepoxide significantly elevated saline consumption. The mechanism for this second effect may have been a retardation in the development of satiety. Finally, at the end of the drinking test, when saline consumption had become satiated, chlordiazepoxide exerted no discernible effect. The enhancement of saline consumption by chlordiazepoxide appears to have been benzodiazepine-receptor mediated, since the effect was reversed by treatment with Ro15-1788, a benzodiazepine receptor antagonist. The implications of a benzodiazepine-induced increase in salt intake are briefly considered. The over consumption of salt is contraindicated in certain clinical conditions. Both stress and hypertension are associated with elevated salt appetite. Treatment of these conditions using benzodiazepines may require due consideration of the possible stimulant effect of these drugs on salt appetite.

Flicker sensitivity changes after subcortical visual system lesions in the rat.

Sensitivity to sinusoidal flicker, as a function of flicker frequency, was measured behaviourally in hooded rats by reducing modulation depth in a two-choice flicker versus no-flicker discrimination until subjects could not perform at above 80% correct. Analogous methods were used to measure spatial contrast sensitivity. In both tasks the display area was 24 x 20 degrees. Bilateral lesions were made in one of 4 structures; superior colliculus (SC), pretectum (PRT), posterior thalamus (PT), or ventral lateral geniculate nucleus (LGv). A fifth group served as sham operated controls. On the basis of histology the LGv group was subdivided according to presence or absence of optic tract damage. PT, PRT and LGv lesions produced a statistically significant depression in flicker sensitivity, the impairment in the LGv sub-group with optic tract damage being significantly greater than that in the LGv group with optic tract sparing. In the latter, post-operative sensitivity correlated significantly with amount of surviving tissue in the thalamic radiations but not with surviving LGv itself. PRT and LGv lesions that involved the optic tract also significantly depressed spatial contract sensitivity. The implications of the finding, that PT and LGv lesions may depress flicker sensitivity without affecting spatial vision, for interpretation of the effects of comparable lesions on suprathreshold discrimination are discussed.

Effects of naloxone and its quaternary analogue on fluid consumption in water-deprived rats.

The effects of subcutaneous administration of naloxone and its quaternary analogue on the consumption of water, saline and saccharin solution were investigated in the water-deprived rat. Quaternary naloxone (0.01-10 mg . kg-1), effective in blocking peripheral opiate receptors, had no effect on fluid intake. In contrast, naloxone (0.01-10 mg . kg-1), produced dose-dependent attenuation of intake for each of the three fluids, indicating a central location of the relevant opiate receptors. Access to saline induced additional drinking, compared with water intake, due to an extension of the initial avid consumption which follows the period of water-deprivation. This enhancement of drinking was blocked by naloxone, but not by its quaternary analogue. Interactions between naloxone and taste factors in drinking may, therefore, depend on blockade of central opiate receptors.

Spatial contrast sensitivity changes after subcortical visual system lesions in the rat.

Spatial contrast sensitivity functions were determined in hooded rats after lesions involving the pretectum (PRT), rostral pretectum and adjacent medial thalamus (PRT +), posterior thalamus (PT), or ventral lateral geniculate nucleus (LGv). PRT and PRT + lesions depressed sensitivity at both high and low spatial frequencies but the high frequency loss was much greater in the latter group. PT lesions depressed sensitivity to frequencies of 0.45 cycles/deg. and above but had no detectable effect upon low frequencies while LGv lesions depressed sensitivity to both high and low frequencies. The discussion relates these results to previous reports of discrimination learning impairments after comparable lesions.

Fluid consumption in water-deprived rats after administration of naloxone or quaternary naloxone.

Water-deprived male rats were given access to water, or to a 0.005M sodium saccharin solution, or to a 0.9% sodium chloride solution, during a 30 min test period. Naloxone (0.01-10.0 mg/kg) produced dose-dependent reductions in the consumption of each fluid. Saccharin-drinking was significantly reduced by 0.01 mg/kg naloxone, and water- and saline-drinking by 0.1 mg/kg naloxone. Quaternary naloxone (0.01-10.0 mg/kg) had no effect on drinking under any condition. Access to the saline solution resulted in hyperdipsia, due to a prolongation of the initial bout of avid drinking in the thirsty rats. Naloxone, in small doses, completely abolished this hyperdipsia. Since the quaternary compound had no effect, it was concluded that opiate antagonist suppression of saline-induced hyperdipsia was probably mediated at central opiate receptors.