Donald A. Czech

Psychophysiological correlates of tonic immobility in the domestic chicken (Gallus gallus)

Abstract Three experiments were conducted measuring within-animal changes in heart rate, respiration rate, and body temperature during tonic immobility. Following immobility onset, heart rate decreased and reached its lowest level just prior to response termination, respiration rate increased initially and then gradually decreased during the immobility episode, while body temperature remained lowered throughout the response period. The results were discussed in relation to the hypothesis that immobility might be related to an aversive emotional state.

Naloxone depresses osmoregulatory drinking in rats

The effect of an opiate antagonist, naloxone, on hypertonic NaCl-induced drinking was studied in rats in a within-subject design. Naloxone reduced drinking at all dosage levels used (0.3-10.0 mg/kg) when compared to a control condition. These results extend previous findings of naloxone mediated reduction in fluid intake in water deprived and osmotically challenged animals. Naloxones effects on fluid intake seems to be independent of procedure employed, and thus quite general. Possible mechanisms were considered.

Naloxone-induced hypodipsia: A CNS mapping study

Opiate antagonists have been shown to reliably attenuate drinking behavior. Recent research points to a central site of action for this antidipsogenic effect. To pursue this issue of site specificity, naloxone, a specific opiate antagonist, was delivered into a number of discrete subcortical areas in 23 hour water-deprived rats. Water intake was measured at 5, 15, 30 and 60 minutes post drug injection. Compared to saline control injections, naloxone reliably depressed water intake, in a dose-related manner, in lateral hypothalamus, preoptic area and zona incerta. Previous research has repeatedly implicated these areas in drinking behavior. Placements which were not generally effective included lateral ventricle, nucleus accumbens, substantia nigra and cortex/corpus callosum. Latency to drink was never affected by any dose of naloxone injected into any site, suggesting an opioid influence on mechanisms involved in termination and/or maintenance rather than on initiation of drinking.

Drinking-induced alterations in reward pathways: an in vivo autoradiographic analysis

An in vivo autoradiographic technique permitted the visualization of discrete neuroanatomical changes in opiate receptor binding as a result of 23-h water deprivation and drinking. Two groups of rats (n = 5) were placed on a 23-h water deprivation schedule for 10 days. On the last day, one group was given access to water for 15 min. These groups, plus a matched ad libitum water control group (n = 5), received an injection of 0.002 mg/kg [3H]diprenorphine ([3H]Dpr) through chronically implanted jugular catheters followed by preparation for opiate receptor autoradiography. Relative cerebral blood flow was estimated non-quantitatively by the injection of 75 microCi/kg iodo-[14C]antipyrene into 3 additional groups identically treated. Results indicated that water-deprivation stress increased [3H]Dpr binding in the claustrum, lateral hypothalamus, amygdala and ventral tegmental area while decreasing binding in the medial frontal cortex, lateral septum, dorsolateral thalamus and central gray. All effects of water deprivation were reversed in animals receiving water. Observations of changes in relative blood flow were shown to have no correlation with changes in opiate receptor binding. It appears that water deprivation stress causes a reduction in opioid release in areas along the mesotelencephalic dopamine pathway which may contribute to a drive state. Water intake may then reduce or otherwise alter the drive state through the release of opioids along these pathways, contributing to the perception of reward.

Nitrous oxide induces an anxiolytic-like effect in the conditioned defensive burying paradigm, which can be reversed with a benzodiazepine receptor blocker

To investigate the anxiolytic effects of nitrous oxide (N2O), male hooded rats were tested in the conditioned defensive burying (CDB) test, a paradigm that exploits a propensity of rats to bury objects associated with aversive stimulation. A single, brief electrical shock was delivered to rats upon contact with an electrified prod, before exposure to one of four mixtures of N2O and oxygen (O2) (10–40% N2O) or room air (RA). Compared to RA-exposed animals, rats exposed to N2O exhibited a concentration-related reduction in duration and height of prod-directed “defensive” burying with floor bedding material; these measures reached statistical significance at 30% N2O. Pretreatment with 20 mg/kg of the benzodiazepine receptor blocker flumazenil, which alone had no effect, effectively antagonized a 30% N2O-induced decrease in burying. Horizontal locomotion and rearing were not significantly affected at concentrations of N2O that attenuated prod-directed burying. Treatment with the benzodiazepine anxiolytic standard, chlordiazepoxide (2.5–10.0 mg/kg) also resulted in dose-related attenuation of burying behavior. These findings show that N2O can induce effects similar to those of known anxiolytics in this paradigm and suggest a benzodiazepine mechanism in its mediation.

Effects of amygdalar lesions on eating and drinking and saline preference in the rat

Abstract Extensive electrolytic lesions were placed bilaterally in the amygdala in albino rats. Both food and water intake relative to preoperative body weight were significantly higher in lesioned animals than in operated controls. Saline preference behavior was also investigated in a two-bottle choice situation. No difference in preference for tap water or a 1.5% NaCl solution was observed between lesioned and control animals.

Possible involvement of nitric oxide in chlordiazepoxide-induced feeding in the mouse

Two experiments investigated a possible role of nitric oxide (NO) in chlordiazepoxide (CP)-induced feeding in nondeprived male ICR mice in independent groups designs. Experiment 1 demonstrated a dose-related decrease in CP-induced solid food intake over a 60-min test period with increasing dose (10, 25, and 50 mg/ kg SC) of the NO-synthase (NOS) inhibitor, L-NG-nitro arginine (L-NOARG), reaching statistical significance at 10 mg/kg L-NOARG when compared to vehicle control. Identical doses of L-NOARG failed to significantly affect normal feeding in vehicle treated mice. In Experiment 2, initial pretreatment with L-arginine (500 and 1000 mg/kg IP) partially or completely restored the feeding inhibitory action of a challenge dose (25 mg/kg SC) of L-NOARG; D-arginine (500 mg/kg IP) was ineffective, thus supporting a stereospecific action of arginine. Arginine isomers did not differentially affect intake in normal feeding animals. These results implicate involvement of NO in CP-induced hyperphagia; they are consistent with and extend research linking NO and ingestive behaviors.

Putative anxiety-linked effects of the nitric oxide synthase inhibitor l-NAME in three murine exploratory behavior models

The aim of the current study was to extend investigation into possible linkage between nitric oxide (NO) and anxiety-linked behavior using a battery of tests. Effects of the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) were investigated in three murine models of anxiety-the light-dark, hole-board and elevated plus-maze-in between-groups designs. Treatment groups included L-NAME (0 [vehicle, or Veh], 10, 25, and 50 mg/kg) and 50 mg/kg of the inactive isomer N(G)-nitro-D-arginine methyl ester (D-NAME) injected subcutaneously. Mice exhibited a robust anxiogenic-like response profile reflected by dose-related decreases in both light-dark (transitions and time in lighted area) and hole-board (head dips and time spent head dipping) test measures, reaching statistical significance at 25 and 50 mg/kg L-NAME when compared to Veh controls (P<.05 or.01; Dunnetts t test), while distance traveled and rearing showed no significant differential pattern in either model. In both models, there was a strong dissociation between nonspecific locomotion and putative exploratory behaviors. D-NAME was not significantly different from Veh condition in either model, indicating a stereospecific action and supporting NO involvement. A dose-related decrease was also observed for several traditional and ethological measures in the plus-maze; however, the effect was limited and relatively weak or absent; with the exception of open-arm and percent open-arm entries, putative anxiety-sensitive measures reached statistical significance only at the highest dose. Reductions in motor activity compromised ability to dissociate an anxiety linkage from a nonspecific motor effect in most measures. It is concluded that the hole-board and light-dark tests provide indication of anxiogenic-like action of NOS inhibition, suggesting that NO has an anxiolytic action. Data from the plus-maze are unclear, owing to a confounding motor influence in most measures.

Benzodiazepine receptor-mediated behavioral effects of nitrous oxide in the rat social interaction test

The present study was conducted to ascertain whether an anxiolytic effect of nitrous oxide was demonstrable in rats using the social interaction test and whether this drug effect might be mediated by benzodiazepine receptors. Compared to behavior of vehicle-pretreated, room air-exposed rats, rat pairs exposed to nitrous oxide showed a generally inverted U-shaped dose-response curve with the maximum increase in social interaction encounters occurring at 25% and significant increase in time of active social interaction at 15-35%; higher concentrations produced a sedative effect that reduced social interaction. Treatment with 5.0 mg/kg of the anxiolytic benzodiazepine chlordiazepoxide also increased social interaction. Pretreatment with 10 mg/kg of the benzodiazepine receptor blocker flumazenil, which alone had no effect, significantly antagonized the social interaction-increasing effects of both nitrous oxide and chlordiazepoxide. In summary, these findings suggest that nitrous oxide produces a flumazenil-sensitive effect comparable to that of chlordiazepoxide and implicate central benzodiazepine mechanisms in mediation of the anxiolytic effect of nitrous oxide.

Drinking behavior is modulated by CNS administration of opioids in the rat.

While opiate antagonists have been shown to reliably attenuate drinking following both central and peripheral administration, relatively few data exist on the effects of agonist agents on this behavior. To address this issue, two opiate agonists, morphine sulfate, a mu agonist, and [D-ala2, D-leu5]-enkephalin (DADLE), a semi-synthetic delta analog of a delta agonist, were administered into several CNS sites in rats. There was a dose-related, naloxone-reversible reduction of water intake following morphine injections into the lateral hypothalamus (LH) and preoptic area (POA). In addition, injections of DADLE also attenuated drinking when injected into LH and POA, but not following the ventral tegmental area or zona incerta administration. These data are discussed in view of a role for the endogenous opioid peptides in the regulation of drinking behavior.