Effects Of Pentobarbital Research Articles

Effect of pentobarbital on postischemic SCH 23390 and rolipram binding in gerbil brain

We investigated the postischemic alterations in dopamine D 1 receptor and Ca 2+/calmodulin independent cyclic adenosine monophosphate (cyclic AMP) selective phosphodiesterase in gerbils and examined the effect of pentobarbital on these alterations. [ 3H]SCH 23390 and [ 3H]rolipram, respectively, were used to label dopamine D 1 receptor and Ca 2+/calmodulin independent cyclic-AMP selective phosphodiesterase. Transient cerebral ischemia was induced for 10 min, and pentobarbital (40 mg/kg) was administered intraperitoneally 30 min prior to ischemia. 5 h after ischemia, [ 3H]rolipram binding decreased significantly in the striatum and hippocampus, whereas no significant change was found in [ 3H]SCH 23390 binding. 7 days after ischemia, however, there was a marked reduction in both [ 3H]SCH 23390 and [ 3H]rolipram binding in the striatum and hippocampus, where histological neuronal damage was found. Pentobarbital significantly ameliorated postischemic decreases in [ 3H]rolipram binding both 5 h and 7 days after recirculation in most areas studied. Furthermore, this drug significantly prevented postischemic reduction in [ 3H]SCH 23390 binding (only) 7 days after ischemia. These results suggest that alteration of cyclic AMP selective phosphodiesterase is more sensitive at an earlier stage after ischemic insult than that of dopamine D 1 receptors. Our results also demonstrate that pentobarbital reduces the alteration in [ 3H]SCH 23390 and [ 3H]rolipram binding after cerebral ischemia.

Reduction of HSP70 and HSC70 heat shock mRNA induction by pentobarbital after transient global ischemia in gerbil brain.

The effect of pentobarbital on the induction of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs after transient global ischemia in gerbil brains was investigated by in situ hybridization using cloned cDNA probes selective for each mRNA species. In sham control brains, HSP70 mRNA was scarcely present, whereas HSC70 mRNA was present in most cell populations. After a 5-min occlusion of bilateral common carotid arteries, HSP70 and HSC70 mRNAs were induced together in several cells and were especially dense in hippocampal dentate granule cells at 3 h, but the strong hybridization of the mRNAs continued only in hippocampal CA1 cells by 2 days. At 7 days after the ischemia, CA1 neuronal cell death was apparent, and the HSP70 mRNA disappeared and HSC70 mRNA content returned to the sham level, except for in the CA1 cells. Pretreatment with pentobarbital (40 mg/kg, i.p.) greatly reduced or inhibited the induction of HSP70 and HSC70 mRNAs at both early (3-h) and late (2-day) phases after ischemia. The drug also prevented CA1 cell death at 7 days along with the maintenance of expression of HSC70 mRNA at the sham control level. Hypothermic effects of pentobarbital were noted at 30 and 60 min after the reperfusion, whereas at 2 h there was no statistical significance between the control and drug-treated groups. The great reduction of HSP70 and HSC70 mRNA induction at both early and late phases after ischemia suggests that pentobarbital reduces intra-and/or postischemic stress and may protect CA1 cells from ischemic damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Antagonism of hypothermia produced by benzodiazepine-related compounds by U-78875 in mice

The benzodiazepine receptor agonists, flurazepam, zolpidem, ZK 93423, and the benzodiazepine inverse agonist, FG 7142, all produced hypothermia when injected i.p. in mice. These compounds are structurally different and do not have the same affinity for the GABA A/benzodiazepine receptor subtypes. Pretreatment with flumazenil (30 mg/kg) completely blocked the hypothermia produced by flurazepam (30 mg/kg), zolpidem (3 mg/kg), and FG 7142 (60 mg/kg), only partially reversed ZK 93423 (3 mg/kg), and was ineffective against 10 mg/kg zolpidem. In comparison, 3 mg/kg of U-78875 completely antagonized all these benzodiazepine agonists. When injected before 30 mg/kg pentobarbital, U-78875 (3 mg/kg) slightly enhanced and prolonged the hypothermic effect of pentobarbital, while flumazenil had very little effect. The results show that U-78875 is a potent antagonist against benzodiazepine receptor agonists, while having demonstrable intrinsic activity.

Acute effects of pentobarbital in a monkey operant behavioral test battery

The effects of acute pentobarbital treatment were assessed using a complex operant test battery containing five tasks in which correct performance is thought to depend upon processes associated with short-term memory and attention [delayed-matching-to-sample (DMTS)], color and position discrimination [conditioned position responding (CPR)], motivation [progressive ratio (PR)], time perception [temporal response differentiation (TRD)], and learning [incremental repeated acquisition (IRA)]. Adult, male rhesus monkeys were tested 15 min after IV injection of saline or pentobarbital (1, 3, 5.6, 10, or 15 mg/kg). Behavioral endpoints measured included percent task completed, response rate or latency, and response accuracy. The order of task sensitivity to disruption by PBT was TRD > IRA = DMTS = PR > CPR, in which sensitivity was defined as a significant disruption in ant aspect of task performance. PBT slowed response rates at 10.0 and/or 15.0 mg/kg in all tasks. Accuracy was decreased in the TRD task at ≥5.6 mg/kg but doses of ≥10.0 mg/kg were required to decrease accuracy in the IRA, DMTS, and CPR tasks. Thus, behavior thought to model time perception (TRD) was more sensitive than behavior modeling learning (IRA), short-term memory and attention (DMTS), and motivation (PR). CPR was the least sensitive behavior. Because pentobarbital exerts its effects at least in part via GABA systems, the effects in the current study were compared with those of a previous study of the acute effects of diazepam. The two compounds exerted fundamentally different effects on operant test battery performance.

Use-dependent pentobarbital block of kainate and quisqualate currents

The effects of pentobarbital on whole-cell excitatory amino acid-induced currents were studies in cultured rat cortical neurons. Currents evoked by 40 μM kainate were reversibly inhibited by pentobarbital with an IC 50 value of 50 μM. The block of the kainate response by pentobarbital was use dependent, requiring kainate stimulation. In the absence of kainate activation, 10 min perfusions of 100 μM pentobarbital inhibited kainate-induced currents less than 10%. Recovery from pentobarbital block also exhibited use dependence, reversing in 5–10 s with kainate stimulation, while persisting 10 min or more in the absence of agonist. Pentobarbital inhibition of the kainate response was not voltage dependent. Responses evoked by 10 μM quisqualate consisted of a peak current desensitizing to a smaller steady-state current. The co-application of 100 μM pentobarbital reduced the steady-state current by49±5%. The peak current before desensitization, however, was inhibited less than 10%. Currents evoked by 25 μM N-methyl- d-aspartate were not significantly inhibited by co-application of 100 μM pentobarbital. The results suggest that the pentobarbital-induced inhibition of kainate responses involves open channel block and that the block of quisqualate currents primarily involve non-desensitizing receptor channels that generate steady-state currents.

Effect of chlormethiazole, dizocilpine and pentobarbital on harmaline-induced increase of cerebellar cyclic GMP and tremor.

Administration to mice of harmaline (100 mg/kg SC) resulted in a greater than two-fold increase in cyclic GMP in the cerebellum 15 min later. This response was inhibited by pretreatment 5 min before the harmaline with pentobarbital (ED50 6.5 mg/kg), chlormethiazole (ED50 10.4 mg/kg) and dizocilpine (ED50 0.5 mg/kg). Harmaline-induced tremor was inhibited by pentobarbital (ED50 30 mg/kg) and chlormethiazole (ED50 50 mg/kg) but not dizocilpine. The data demonstrate that the harmaline-induced tremor and cerebellar cyclic GMP rise are probably not associated. They also demonstrate that chlormethiazole is able to inhibit a biochemical response (the increase in cerebellar cyclic GMP) which results from increased glutamate function.

A new highly sensitive procedure--a prerequisite to evaluate the density of GABAA receptors and to study their allosteric properties in distinct areas of rat brain.

A new procedure for tissue preparation is described for the study of modulatory effects of neuroactive steroids and barbiturates on the in vitro binding of [3H]muscimol in distinct areas of rat brain. This method had been optimized for the highest amount of [3H]muscimol binding and a maximal effect of pentobarbital on radioligand binding. The following steps like tissue freezing, initial homogenization in alkaline triethanolamine buffer (pH 9.0), fractionated centrifugations and washings of the resulting membrane fractions in disodium piperazine-N-N'-bis[2-hydroxypropanesulfonic acid] buffer (pH 7.4) provided the best results. In spite of a shorter time of preparation compared to preparative techniques traditionally used our procedure yields GABAA receptor sites with a higher sensitivity to the binding of muscimol without affecting their allosteric properties thereby allowing the use of minute brain tissue samples as little as 50mg wet weight. The GABAA receptor sites of the resulting membrane fractions are viable as muscimol binding had a higher affinity in cerebellum (CER) (KD = 6.9 +/- 1nM) than frontal cortex (FC) (KD = 18.4 +/- 1.4nM) which is in the range of highly purified receptors; CER was significantly more densely labelled than FC; the IC50 value of 2 x 10(-7) M for bicucullin-methiodide and the magnitude of the effect of pentobarbital are similar to published results. The rapid modulatory onset of the action of 3-alpha-hydroxy-5-alpha-pregnane-20-one (HPO) which was effective after a preincubation of only 30s as well as the threshold concentration of 10nM HPO for enhancement of the binding of muscimol provided evidence for the high sensitivity of GABAA receptors to neuroactive steroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Limited but evident protective effects of MK-801 and pentobarbital on neuronal damage following forebrain ischemia in the gerbil under normothermic conditions

The purpose of this study was to examine the protective effects of an N- methyl- d-aspartate receptor antagonist, MK-801, and pentobarbital against neuronal damage in a global ischemia model under controlled body temperature. Gerbils were subjected to 3 and 5 min of bilateral common carotid artery occlusion. MK-801 (1 and 5 mg/kg, i.p.), administered 30 min before ischemia, significantly attenuated the degeneration of hippocampal CA1 pyramidal cells after 3 min of ischemia in a dose dependent manner, but had no such effects after 5 min of ischemia. Pentobarbital (40 mg/kg, i.p.) also protected against CA1 damage after 3 min of ischemia but not after 5 min of ischemia. Thus, we confirmed the protective effects of these agents under normothermic conditions, although these effects were limited to shorter periods of ischemia.

Effect of Nimodipine, Phenylephrine, Pentobarbital, and Ketamine on Cerebral Energy Metabolism in Cerebral Air Embolized Cats: in vivo 31 P Nuclear Magnetic Resonance Spectroscopy Study

Effect of Nimodipine, Phenylephrine, Pentobarbital, and Ketamine on Cerebral Energy Metabolism in Cerebral Air Embolized Cats: in vivo 31 P Nuclear Magnetic Resonance Spectroscopy Study

The prolongation effect on the duration of pentobarbital anesthesia by submaxillariectomy in male rats

The present study was performed to investigate the effects of submaxillariectomy (Subx) on the anesthetic effect (sleeping time) of pentobarbital, the concentration-time profile of plasma pentobarbital and the hepatic drug metabolizing enzyme systems in male rats of the Donryu strain. Subx was performed when the rats were 60 days old. Subx prolonged the duration of pentobarbital (30 mg/kg, i.p.) anesthesia at 10, 23 and 43 days after the operation, respectively. At 43 days after Subx, the plasma pentobarbital concentration was higher in the Subx group until 30 min after the administration. There was no significant difference in the hepatic microsomal cytochrome P-450 content between the Subx and control groups. Cytochrome b5 content, aminopyrine N-demethylase and aniline hydroxylase activities were increased significantly in the Subx group. The activity of heme oxygenase, the rate limiting enzyme in the heme catabolic pathway, tended to increase in the Subx group. Furthermore, the activity of delta-aminolevulinic acid synthetase, the rate limiting enzyme in the heme synthetic pathway, was significantly decreased to 51 percent of the control group by Subx. These results may suggest that the prolongation of the duration of pentobarbital anesthesia is caused by Subx due to the change in the pharmacokinetics of pentobarbital, especially the inhibitory effects of the hepatic pentobarbital metabolizing enzyme system.

Postischemic alteration of muscarinic acetylcholine and adenosine A1 binding sites in gerbil brain

We studied the alterations in the binding of muscarinic cholinergic and adenosine A1 receptors following transient cerebral ischemia in Mongolian gerbils and examined the effects of the novel vinca alkaloid derivative vinconate and pentobarbital against the alterations in the binding of these receptors. Animals were allowed to survive for 5 h and 7 days after 10 min of cerebral ischemia induced by bilateral occlusion of common carotid arteries. [3H]Quinuclidinyl benzilate (QNB) and [3H]cyclohexyladenosine (CHA) were used to label muscarinic cholinergic and adenosine A1 receptors, respectively. The [3H]QNB and [3H]CHA bindings showed no significant alteration in the gerbil brain 5 h after ischemia. However, these bindings in the striatum, the hippocampal CA1 sector, and the hippocampal CA3 sector revealed a significant reduction 7 days after ischemia. The [3H]CHA binding also showed a significant decline in the dentate molecular layer 7 days after ischemia. Intraperitoneal application of vinconate (100 and 300 mg/kg) 10 min and pentobarbital (40 mg/kg) 30 min before ischemia showed a mild reduction in the [3H]CHA binding in the brain 5 h after ischemia. Especially, the reduction was found in the hippocampal CA1 sector and the dentate molecular layer. However, the [3H]QNB binding revealed no significant alteration in the brain 5 h after ischemia. Seven days after ischemia, both drugs prevented a marked reduction in the [3H]CHA binding in the striatum, but not in the hippocampal CA1 sector, the hippocampal CA3 sector, and the dentate molecular layer. By contrast, vinconate and pentobarbital failed to prevent the reduction in the [3H]QNB binding in the striatum. Morphological study indicated that vinconate and pentobarbital ameliorated the neuronal damage to the striatum, but not the hippocampal damage 7 days after ischemia. This histological finding was relatively consistent with the alteration in the [3H]CHA binding. These receptor autoradiographic and histological data suggest that vinconate and pentobarbital can protect the brain from both cellular and functional consequences of ischemia. These findings are of interest in relation to the mechanisms of ischemic brain damage.

Effects of d-amphetamine, WIN 35,428, pentobarbital and morphine on schedule-controlled responding in two inbred rat strains that differ in locomotor stimulatory effects of cocaine

Behavioral effects of d-amphetamine, the cocaine analog, WIN 35,428, morphine, and pentobarbital were compared in NBR/NIH and F344CR1BR rats. Either nose-poke or lever-press responding was maintained under 3-min fixed-interval schedules of food presentation. The effects of morphine, WIN 35,428 and pentobarbital depended upon the rat strain studied: morphine increased nose-poke responding in NBR but not F344 rats; significant strain x dose interactions were observed with WIN 35,428; and pentobarbital was more potent in decreasing nose-poke responding in NBR than in F344 rats. No strain differences were observed in the behavioral effects of d-amphetamine. There were also prominent differences in the effects of drugs that were related to the nature of the response requirement. In both rat strains, nose-poke responding was affected differently than lever-press responding by morphine, d-amphetamine, and WIN 35,428. Pentobarbital produced effects that were independent of the specified response topography. A global underlying difference in these rat strains cannot be identified at present to account for the diversity of findings. The behavioral effects of these drugs appear to be influenced by a host of interactive factors including the drug, strain of animal, the baseline response rate and physical dimensions of the response.

Dehydroepiandrosterone enhances the hypnotic and hypothermic effects of ethanol and pentobarbital

Recent reports have indicated that the neurosteroid dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) interact with the GABA A receptor complex. Because many of the behavioral effects of ethanol and pentobarbital are due to activity at this complex, DHEA and DHEAS were tested for their ability to interact with the hypnotic and hypothermic effects of ethanol and pentobarbital. DHEA, but DHEA and DHEAS themselves cause a fall in body temperature. DHEA enhances the hypothermic effect of both ethanol and pentobarbital. DHEAS enhances the hypothermic effect of ethanol, but with pentobarbital it only delays the return of body temperature to baseline levels. Neither DHEA nor DHEAS affects the metabolism of ethanol.

Interaction of pregnanolone and pregnenolone sulfate with ethanol and pentobarbital

3-α-Hydroxy-5-β-pregnan-20-one [pregnanolone (Pa)] and 3-β-hydroxy-5-pregnen-20-one 3-sulfate [pregnenolone sulfate (PS)] are steroids that have been shown in biochemical studies to be active at the GABA-benzodiazepine-chloride receptor complex, Pa as a “barbiturate-like” agonist and PS as a “picrotoxin-like” antagonist. Since other compounds that are active at this site interact with the effects of pentobarbital and ethanol, the behavioral effects of these steroids alone and in combination with pentobarbital and ethanol were tested. Pa blocks the convulsions caused by pentylenetetrazole (PTZ) and increases motor activity when given alone in low doses. In combination with either pentobarbital or ethanol, it enhances the depression in motor activity, hypothermia, and hypnosis. In contrast, PS has no effect on PTZ convulsions and depresses motor activity by itself. With pentobarbital, PS enhances the depression in motor activity but has no effect on hypothermia or hypnosis. With ethanol, PS enhances the hypothermia but does not affect motor activity or hypnosis. Therefore, Pa and PS show different but no opposite effects in interacting with compounds active at the GABA-benzodiazepine-chloride receptor complex.

Selective effects of pentobarbital and halothane on c-fos and jun-B gene expression in rat brain.

The effects of pentobarbital and halothane anesthesia on the expression in brain of the immediate-early genes c-fos and jun-B were investigated. Pentobarbital-anesthetized rats (n = 10) received a single intraperitoneal injection of pentobarbital 65 mg/kg in a vehicle of 40% propylene glycol and 10% ethanol and then were placed in a plexiglass box flushed continously with 100% oxygen at 5 l/min. Halothane-anesthetized rats (n = 10) received an intraperitoneal injection of vehicle only and were transferred to a box flushed continuously with oxygen plus 1.5% halothane. Unanesthetized control rats (n = 10) received an intraperitoneal injection of vehicle and were placed in a box flushed continuously with 100% oxygen. Four additional rats received no intraperitoneal injection but were handled and otherwise treated identically to the control group, and six others had a femoral arterial catheter inserted for blood pressure and blood gas measurements. Five animals from the control and both anesthetized groups were killed at 30 and 120 min postinjection and their brains rapidly removed and frozen. The messenger ribonucleic acid transcription products of the genes c-fos, jun-B, and beta-actin from whole cerebral hemispheres were analyzed autoradiographically after Northern blot hybridization with 32P-labeled deoxyribonucleic acid probes. Relative levels of c-fos and jun-B messenger ribonucleic acid were determined from optical density measurements of the autoradiographic bands, with beta-actin measurements being used to correct for sample-to-sample variation. Rats became immobile within minutes of drug administration and remained anesthetized until they were killed.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of sedatives on GABA-mediated chloride flux into cerebral cortical microsacs prepared from emotional and non-emotional mice

Some strains of rats and mice express increased momentary fear or emotionality when exposed to a novel environment. Previous studies have found significantly fewer diazepam binding sites in the brains of Balb/cJ mice compared to C57BL and AKR/J mice and this has been suggested to contribute to the increased emotionality of the ‘nervous’ Balb strain. The influx of 36Cl into cerebral cortical microsacs was used to functionally assess the effects of GABA, diazepam and pentobarbital in the Balb mice compared to nonemotional animals (C57 and ICR mice). Slight differences in the ability of GABA to increase chloride influx were found among the three strains. Pentobarbital potentiation of GABA-mediated chloride flux was slightly higher in the ICR mice compared to Balb and C57. Diazepam potentiation of the effects of GABA, however, was significantly decreased in the Balb mice, strengthening the hypothesis that the benzodiazepine receptor is involved in mediating animal emotionality.

Cholinomimetic activity of minaprine is related to the amelioration of delayed neuronal death in gerbils

We attempted to determine if the cholinomimetic activity of the psychotropic drug minaprine was related to the amelioration of the delayed neuronal death induced by cerebral ischemia in Mongolian gerbils. Minaprine improved the passive avoidance deficit induced by cerebral ischemia, and the histopathological ischemic neuronal changes in the hippocampal CA1 neurons were diminished. These effects were completely inhibited by treatment with the cholinergic blocker scopolamine. Rectal temperature fell about 1.5°C immediately after cerebral ischemia and hyperthermia occurred 30 and 60 min after recirculation. Minaprine had no effect on body temperature before or after ischemia. Physostigmine and tetrahydroaminoacridine (THA), drugs which stimulate the cholinergic system, improved passive avoidance deficits and prevented the delayed neuronal death. These effects of physostigmine and THA were completely inhibited by scopolamine. Pentobarbital and diazepam also improved the passive avoidance deficit and prevented the destruction of CA1 neurons. In contrast with minaprine, these effects of pentobarbital and diazepam were not inhibited by scopolamine. As the protective effect of minaprine against ischemia-induced delayed neuronal death is related to cholinomimetic activities, these events differ from those seen with pentobarbital and diazepam.

Perinatal Protein Deprivation Enhances the Anticonflict Effect Measured after Chronic Ethanol Administration in Adult Rats

The anticonflict effects of ethanol, diazepam and pentobarbital were evaluated in adult rats fed a low protein diet during the perinatal period in the plus-maze test, after single injections and following chronic ethanol administration (1 g·kg-1·d-1 for 30 d). Reactivity to the anticonflict effect of these drugs was similar in control and protein-deprived rats after acute treatment. After chronic ethanol administration, control rats showed tolerance to ethanol and cross-tolerance (i.e., lower reactivity) to the anxiolytic effect of diazepam and pentobarbital. Conversely, protein-deprived rats showed greater reactivity to ethanol and lack of cross-tolerance to diazepam and pentobarbital following chronic ethanol treatment. A significantly greater density of cortical γ-aminobutyric acid receptors subtype A (GABA-A) was detected in protein-deprived rats after chronic ethanol administration compared with the density after chronic saline treatment, whereas no differences were observed in nourished controls. This suggests that the greater anxiolytic activity detected in protein-deprived rats may correlate with higher GABA-A receptor density.

Effects of pentobarbital on heterosegmentally activated dorsal root depolarization in the rat. Investigation by sucrose-gap technique in vivo.

Slow positive cord dorsum (P-) potentials activated by segmental stimulation are believed to reflect primary afferent depolarizations and have been shown to be augmented by barbiturates. However, there have been no data to confirm whether heterosegmentally activated P-potentials also represent primary afferent depolarizations and are similarly affected by barbiturates. We therefore tested whether heterosegmental P-potentials reflect primary afferent depolarizations and how these heterosegmental potentials are affected by barbiturates. Heterosegmentally activated dorsal root (DR) depolarizations (depolarizations evoked in DRs of lumbar segments in response to afferent volleys to cervical segments produced by electrical stimulation of the forepaw) and P-potentials were simultaneously recorded, adapting the sucrose-gap technique for recording DR depolarization in vivo in the rat. Forepaw (heterosegmental) stimulations produced a large depolarization in the DRs of L5-S1 as well as a slow P-potential in the lumbosacral enlargement. Transection of the spinal cord at the level of C1-C2 abolished both the P-potential and DR depolarization activated by heterosegmental stimulation as well as the second component of segmentally (hind-paw) activated P-potential. Bicuculline (100 micrograms/kg, intravenous) augmented the P-potential and DR depolarization produced by heterosegmental stimulation, but larger doses, 400-600 micrograms/kg, eventually suppressed these. However, the drug, in a dose-dependent manner, suppressed both the P-potential and DR depolarization produced by the segmental stimulation. Pentobarbital (10-40 mg/kg, intravenous) suppressed in a dose-dependent manner both the heterosegmental P-potential and heterosegmental DR depolarization and prolonged their peak latencies. By contrast, pentobarbital augmented and prolonged the segmental P-potential and segmental DR depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

Sodium pentobarbital: sensory and associative effects in classical conditioning of the rabbit nictitating membrane response.

Four experiments were conducted to determine the effects of sodium pentobarbital (0, 3, 9, and 15 mg/kg) on the acquisition of the rabbit's classically conditioned nictitating membrane response (NMR) and to determine the locus of the drug's effects on sensory, motor, associative, and nonassociative processes. In experiment 1, classical conditioning of the NMR was accomplished by pairing tone and light conditioned stimuli (CSs) with paraorbital shock as the unconditioned stimulus (US). The experiment revealed that pentobarbital retarded the acquisition of conditioned responses (CRs) to both tone and light CSs. Experiment 2, employing unpaired CS, UCS presentations, indicated small but significant drug effects on NMR base rate and nonassociative NMRs to the CS. Experiment 3 revealed no significant drug effect on the psychophysical functions relating UCS intensity to UCR frequency or amplitude, nor on the UCS intensity threshold for eliciting UCRs. On the other hand, in experiment 4, the drug significantly impaired CR frequency over an extended range of CS intensities and raised CS intensity threshold. It was concluded that pentobarbital's attenuation of CS intensity also operated to impair CR acquisition.