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Biomedical subjects

K A Miczek

Publications and source records attributed to K A Miczek.

At least 55 records · Page 3Linked to original sources
PubMed1998

Aggressive and social behavior after alprazolam withdrawal: experimental therapy with Ro 19-8022.

The aim of the present study was to ascertain whether withdrawal from alprazolam can increase anxiety-like and aggressive behavior during intra species conflict in mice and, if so, whether a partial benzodiazepine agonist Ro 19-8022 is able to reverse these behavioral changes without untoward effects such as sedation. An experimental model consisting of interactions of pairs of singly-housed male mice with non-aggressive group-housed male mice was used. Alprazolam (1 mg/kg) was given orally twice daily for 8 days and once on the 9th day. When withdrawn from alprazolam (3 days after the last dose), mice reduced social investigation and increased the incidence of aggressive behavior in comparison to the pre-withdrawal level. However, the increase of aggression was moderate and occurred only in subjects with low pre-treatment levels of aggression. Ro 19-8022 (10 mg/kg) significantly antagonized the decrease of social behavior and the increase of aggression after alprazolam withdrawal without causing sedation or ataxia.

Aggression↗
PubMed1998

Ultrasonic vocalizations in rat pups: effects of serotonergic ligands.

Ligands with varying intrinsic activity and selectivity for the various subtypes of the serotonin receptor were tested in the rat pup ultrasonic vocalization (USV) model, a putative animal model reflecting anxiety. USV were elicited by isolating rat pups from their mother and littermates by placing them on a warm (37 degrees C) or a cold (18 degrees C) plate. Concurrently, the negative geotaxic (NG) response and rectal temperature were determined to assess the potentially sedative and hypothermic effects of putative anxiolytics. USV were reduced at low doses and in both temperature conditions by the full 5-HT1A receptor agonists flesinoxan and 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin.HBr) and the partial 5-HT1A receptor agonists buspirone, ipsapirone and BMY 7378 (2-[4-[4-[2-pyrimidinyl]-1,2-piperazinyl]butyl]-1,2-benzi-isoth iozol-3-(2H)one-1,1-dioxide. 2HCl). The 5-HT1A receptor antagonists NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phtalimido)-butyl]piperazide.2H Cl), (+/-)-WAY 100,135 (+/-)-(N-tert-butyl-3(4-(2-methoxy phenyl)piperazin-1 -yl)-2-phenyl propionamine.2HCl), and ((S)-UH-301 (S)-5-fluoro-8-hydroxy-2-(di-n-propyl-amino)tetralin.HBr) reduced USV at higher doses and only in one of both test conditions. The selective 5-HT1A receptor antagonist DU 125530 (2-[4-[4[(7-chloro-2,3dihydro-4-benzodioxin-5-yl)-1-piperazi nyl]butyl]-1,2-benzisothiazol-3(2H)-one-1,1, dioxide, monomesylate), did not influence USV at the cold plate up to high doses, although concomitantly the negative geotaxis was disturbed. The negative geotaxis was impaired after all 5-HT1A receptor ligands, except BMY 7378 and (+/-)-WAY 100,135. Hypothermia coincided with USV-suppression, except for NAN-190 and (S)-UH-301. The USV-suppressing action of flesinoxan (3 mg/kg) could be antagonized by DU 125530, but not its NG effect. However, the hypothermia induced by flesinoxan was antagonized by DU 125530. USV were also suppressed by the 5-HT uptake inhibitors fluvoxamine (both warm and cold plate) and clomipramine (only warm plate). The tricyclic antidepressant imipramine only decreased USV on the cold plate, however, in a U-shaped dose-response curve. At the highest dose tested, no decrease was present. The 5-HT uptake stimulant tianeptine reduced USV under both conditions. Fluvoxamine had no side effects, clomipramine induced hypothermia and tianeptine clearly had sedative properties. The 5-HT1B/2C receptor agonist TFMPP (trifluorometaphenylpiperazine) stimulated USV at a low dose at the cold plate and suppressed USV at a high dose under both conditions. The 5-HT2A/2C receptor antagonist ketanserine enhanced USV at low doses under both conditions and had no effect at a higher dose. Concurrently heavy sedation and hypothermia occurred. The 5-HT3 receptor agonist phenylbiguanide and the 5-HT3 receptor antagonist ondansetron had no effect in this paradigm. Clearly, subtypes of the 5-HT receptor affect rat pup USV differentially.

Animals↗
PubMed1998

Essential roles for the Abl and Arg tyrosine kinases in neurulation.

The Abl and Arg tyrosine kinases play fundamental roles in the development and function of the central nervous system. Arg is most abundant in adult mouse brain, especially in synapse-rich regions. arg(-/-) mice develop normally but exhibit multiple behavioral abnormalities, suggesting that arg(-/-) brains suffer from defects in neuronal function. Embryos deficient in both Abl and Arg suffer from defects in neurulation and die before 11 days postcoitum (dpc). Although they divide normally, abl(-/-)arg(-/-) neuroepithelial cells display gross alterations in their actin cytoskeleton. We find that Abl and Arg colocalize with each other and with actin microfilaments at the apical surface of the developing neuroepithelium. Thus, Abl and Arg play essential roles in neurulation and can regulate the structure of the actin cytoskeleton.

Actins↗
PubMed1998

Ethanol drinking in socially housed squirrel monkeys.

This study proposes a method to assess voluntary alcohol drinking in socially living squirrel monkeys. Group-housed squirrel monkeys were induced to drink a sucrose solution and subsequently an ethanol/sucrose solution in an experimental chamber attached to the home colony room, allowing the daily intake to be monitored for each individual without disrupting the social context. Sucrose concentration (0.03-0.6 M, corresponding to 1-20%) and ethanol concentration (0-4%) were gradually increased in tap water and in a 0.6 M (ca. 20%) sucrose solution during daily 30-min and 10-min sessions, respectively. Blood ethanol levels ranged from 10-50 mg/dl and remained below intoxication level. These experiments demonstrate that it is feasible to arrange conditions under which individual socially housed squirrel monkeys voluntarily drink a sweetened ethanol solution.

Alcohol Drinking↗
PubMed1998

Alcohol and heightened aggression in individual mice.

The objective of the current research was to study the large individual differences in alcohol effects on aggressive behavior under systematically varied conditions in experimental protocols with mice. Three experiments were conducted with outbred Swiss-Webster derived mice that identified those individuals whose aggressive behavior was reliably heightened by low acute alcohol doses. In all experimental protocols, low alcohol doses were orally administered to a "resident" male mouse that subsequently confronted an "intruder" opponent for 5 min while all salient elements of aggressive behavior and motor activities were quantified. In all three experiments, alcohol (1.0 g/kg) heightened aggressive behavior by at least two standard deviations of the individual's water vehicle control mean in 27% of the mice. In 64% of mice, no reliable change in aggressive behavior was detected after the identical alcohol treatment, and in 9% of the mice alcohol decreased aggressive behavior. Experiments differed in protocol indicating that these aggression-heightening effects were evident in resident mice that were either maintained at restricted or unlimited amounts of food, housed singly or in breeding pairs with a female partner, and conditioned to perform daily a food-reinforced task or remained undisturbed. The first experiment found the aggression-heightening effects to persist during weekly challenges for at least 2 months (n = 8 of 30). The second experiment showed these effects at intervals from 5 to 60 min after alcohol administration. Blood alcohol concentrations reached peak level within 5 to 10 min after oral administration in mice that had confronted an intruder. Those mice in whom alcohol heightened aggressive behavior (n = 21) did not differ from those that showed suppressed levels (n = 9) in terms of blood alcohol concentrations (79.6 vs. 82.4 mg%), suggesting that the intensity and frequency of aggressive behavior after alcohol were not directly dependent on the amount of alcohol in the circulation. The third experiment revealed that alcohol's (0.1 to 5.6 g/kg) effects on heightened aggressive behavior (n = 11) are dissociated from those on concurrently measured high- or low-rate operant performance as engendered by a multiple FR 30-FI 600 sec schedule of reinforcement. Current results indicate that this alcohol effect is relatively specific to aggressive behavior in individual animals, offering the opportunity for neuropharmacological and molecular characterization.

Aggression↗
PubMed1997

Alcohol, GABAA-benzodiazepine receptor complex, and aggression.

Neurobiological investigations have become productive since experimental protocols were developed that engender large increases in aggressive behavior after acute alcohol challenges in individual experimental animals. Recent developments extended the heightened aggressive behavior to rats that self-administered alcohol shortly before the social confrontation. Quantitative ethological analysis revealed that alcohol prolongs "bursts" of aggressive acts and displays and disrupts communication between the aggressive animal and the opponent who defends, submits, or flees. Pharmacological modulation of the GABAA receptor with benzodiazepine agonists and neuroactive steroids results in dose-dependent biphasic changes in aggressive behavior that mimic the dose-effect function of alcohol; benzodiazepines potentiate the aggression-heightening effects of alcohol as well as the behaviorally suppressive effects; and antagonists at benzodiazepine receptors prevented the aggression-heightening effects of alcohol. The maturational and experiential origins for potentially distinctive GABAA receptor characteristics in individuals who exhibit heightened aggressive behavior await identification.

Aggression↗
PubMed1997

Acquisition of cocaine self-administration after social stress: role of accumbens dopamine.

Exposure to either aversive or rewarding environmental stimuli increases extracellular dopamine (DA) concentrations in terminal areas of the mesocorticolimbic dopamine system. Furthermore, behavioral reactivity to an environmental stressor has been shown to correlate with latency to initiate self-administration of psychomotor stimulant drugs. The present study examined the behavioral and dopaminergic responses of rats to social defeat stress and compared latencies to initiate cocaine self-administration in defeated and non-defeated rats. In vivo microdialysis was used to examine the effects of social defeat stress on DA concentrations in nucleus accumbens of freely-moving rats. During the experimental session, dialysate and video recording samples were collected from previously-defeated and non-defeated "intruder" rats in consecutive phases, while (1) in the home cage, (2) when placed in the empty, soiled cage of a resident rat which had previously defeated them, and (3) when exposed to threat of defeat by the resident. Immediately following threat of defeat, previously-defeated and non-defeated intruders were given the opportunity to self-administer cocaine IV. When exposed to the olfactory cues of an aggressive resident, extracellular DA levels in nucleus accumbens increased to approximately 135% of baseline in previously defeated rats versus 125% of baseline in non-defeated rats. When exposed to social threat by the resident, DA levels further increased to 145% of baseline in previously defeated rats versus 120% in non-defeated rats. Previously defeated rats acquired cocaine self-administration in approximately half the time of non-defeated rats, consistent with the hypothesis that prior stress exposure may induce a cross-sensitization to the rewarding effects of cocaine. These results are consistent with the idea that exposure to stress may induce changes in central dopaminergic activity, which may render an individual more vulnerable to acquiring psychomotor stimulant self-administration.

Animals↗
PubMed1997

Increased aggression after ethanol self-administration in male resident rats.

In order to study experimental alcohol intake that leads to heightened aggression, we established ethanol self-administration in aggressive rats. The focus was on low doses of self-administered ethanol and to assess their effects on aggressive behavior in resident rats, using a limited access paradigm followed by a 5-min confrontation with an intruder. In the first phase of the experiment, rats were established as "residents", and their consistent aggressive behavior in confrontations with an intruder was verified. In the second phase, these resident rats were trained to self-administer alcohol, using a sucrose-fading technique. In the third phase, alcohol self-administration was followed by intruder confrontations in order to study the effect of alcohol on aggression. Confrontations after ethanol consumption leading to low (5-20 mg/dl) and moderate (20-50 mg/dl) blood alcohol concentration (BAC) were compared to confrontations without alcohol, each animal serving as its own control. On average, the group showed no change in aggressive behavior after low or moderate ethanol intake. However, six out of 16 individuals significantly increased the number of attack bites and the duration of aggressive behavior by up to 90% after alcohol self-administration. When these rats were assigned post-hoc to an alcohol heightened aggression group, the group was characterized by a 40% increase in number of attack bites and a 90% increase in aggressive posture over control (BAC 0 mg/dl), whereas the alcohol non-heightened aggression group showed no significant changes. These results extend previous observations of increased aggression in a subpopulation of animals after experimenter-administered ethanol in mice, rats and monkeys to self-administered alcohol. Using this animal model, individuals showing enhanced or reduced aggression after oral alcohol self-administration can be characterized behaviorally, physiologically, and neurochemically.

Aggression↗
PubMed1997

Ultrasonic vocalizations in rat pups: modulation at the gamma-aminobutyric acidA receptor complex and the neurosteroid recognition site.

Agonists acting at benzodiazepine, gamma-aminobutyric acidA, barbiturate and neurosteroid recognition sites were studied for their attenuation of separation-induced ultrasonic vocalizations (USV) in rat pups. The behavioral effects of the neuroactive steroid 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone) were assessed when the drug was administered alone and in combination with agonists and antagonists acting at the gamma-aminobutyric acidA receptor complex. At 7 days postpartum, male and female Long-Evans rat pups were separated from the dam and littermates, and placed on a 20 degrees C surface for 2 min. Allopregnanolone (1-30 mg/kg s.c.), alprazolam (0.03-1 mg/kg s.c.), diazepam (0.1-3 mg/kg s.c.), muscimol (0.03-0.3 mg/kg s.c.) and pentobarbital (1-30 mg/kg s.c.) dose-dependently decreased USV. Pretreatment with flumazenil (0.1 mg/kg s.c.) antagonized alprazolam's and diazepam's USV-suppressive effects; bicuculline (2 mg/kg s.c.) reversed muscimol's USV-suppressive effects. Allopregnanolone (3 mg/kg s.c.) produced a 4- to 7-fold leftward shift in alprazolam's and diazepam's USV-suppressive effects, and also produced a modest leftward shift in pentobarbital's USV dose-effect function. Neither flumazenil, bicuculline, nor picrotoxin (1 mg/kg s.c.) altered allopregnanolone's USV-suppressive effects. These results suggest that the USV-suppressive effects of the neurosteroid allopregnanolone are mediated at the gamma-aminobutyric acidA receptor complex, and are independent from a direct action on the benzodiazepine or gamma-aminobutyric acidA recognition sites on this complex.

Alprazolam↗
PubMed1996

Social defeat stress selectively alters mesocorticolimbic dopamine release: an in vivo microdialysis study.

Exposure to various aversive stimuli ('stressors') as well as positively-reinforcing stimuli has been shown to increase extracellular dopamine concentrations in terminal areas of the mesocorticolimbic dopamine system. The magnitude and site specificity of the dopaminergic response may depend on the nature of the aversive stimulus. In the present study, in vivo microdialysis was used to examine the effects of an ethologically relevant stressor, namely threat of social defeat, on dopamine concentrations in nucleus accumbens, striatum, and prefrontal cortex of freely-moving male Long-Evans rats. During the test session, dialysate and video recording samples were collected from previously-defeated 'intruder' rats in consecutive phases, while (1) in the home cage, (2) when placed in the empty, soiled cage of a resident rat which had previously defeated them, (3) when exposed to threat of defeat by the resident, and (4) when returned to their home cages. Control animals were not defeated; in this group of rats video recording and dialysate samples were obtained when they were placed into an empty, clean novel cage and later returned to their home cage. The results indicated that levels of dopamine were elevated to approximately 130% of baseline in nucleus accumbens and prefrontal cortex when rats were placed into either the resident or novel cage. In defeated intruders, extracellular dopamine levels in accumbens and prefrontal cortex were increased further (approximately 160% of baseline), during social threat; these biochemical changes were synchronous with high levels of orienting toward the resident but not with heightened motor activity. Extracellular dopamine levels in lateral striatum were not affected by either manipulation. These results suggest that altered accumbens and cortical extracellular dopamine concentrations during social threat are not secondary to motor activation but instead reflect increased attention to the provocative stimulus or attempts by the intruder to 'cope' with the stimulus.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Withdrawal from oral cocaine in rate: ultrasonic vocalizations and tactile startle.

While anxiety appears to characterize humans who administer high doses of cocaine or experience withdrawal from cocaine, it is difficult to capture this aspect of cocaine effects in animals. The present study investigated if acute or protracted withdrawal from prolonged low-dose cocaine that is self-administered via the oral route could be detected in tactile startle and vocal "distress" responses of rats. Adult, male Long-Evans rats had access to cocaine solution (0.1 mg/ml) either for 24 or 4 h/day using the two-bottle choice technique. The amount of solution consumed from each bottle was measured daily for 30 or 60 days. On days 1, 3, 7, 14, 21, 28 of withdrawal, startle and ultrasonic vocal responses (USV, 15-35 kHz) were measured in response to 18 air-puff stimuli (20 psi). Rats drank an average of 5-20 mg/kg per day of the cocaine solution. On average, about half of the daily liquid was consumed from the cocaine solution-containing bottle. USVs were emitted at significantly increased rates on day 3 of withdrawal from 30 or 60 days of cocaine drinking. Startle reactions were slightly, but non-significantly increased on day 1 of withdrawal. Comparable to withdrawal from ethanol, morphine, and diazepam treatments, withdrawal from oral self-administration of low to moderate doses of cocaine increases the rate of ultrasonic vocalizations while increasing minimally the amplitude of startle responses to low-intensity tactile stimuli. Nevertheless, no correlation between the total amount of cocaine self-administered or the duration of treatment with the intensity of the withdrawal manifestations could be detected.

Animals↗
PubMed1996

Activational effects of social stress on IV cocaine self-administration in rats.

The objective of the current studies was to investigate how social stress modulates IV cocaine self-administration. Specifically, an experimental protocol was developed in rats that assessed the impact of recurrent non-injurious social confrontations with an aggressive opponent on subsequent rate of cocaine self-administration behavior, maintained across a range of doses. Initially, the cocaine dose-effect function for intravenous self-administration was determined, reinforcing every fifth lever press (fixed ratio or FR 5), with each dose (0.031, 0.063, 0.125, 0.25 mg/infusion and saline) being assessed for at least 3 days. Subsequently, the rats were assigned to two groups, one group being exposed as intruders to the threats of an aggressive resident rat for 60 min, while being protected by a screen, immediately before a session for IV self-administration with maximally 15 cocaine infusions. A second group served as control, being determined for a second cocaine dose-effect function without any social stress exposure. Additional rats performed conditioned lever pressing that was reinforced by food at a rate and pattern closely similar to that characteristic for cocaine IV self-administration (joint FI 3 min FR 5). Recurrent episodes of mild social stress increased the rate of responding on the cocaine-reinforced lever. This increase is seen after rats have been exposed to the threats of an aggressive opponent, but not after social or single housing. These behaviorally activating effects of social stress (1) are long-lasting, (2) are not subject to habituation, (3) are selective to responding that is reinforced by IV cocaine, do not extend to non-reinforced lever pressing, or to food-reinforced lever pressing, (4) are most prominent in the time-out period during and after the cocaine infusion, (5) do not shorten the intervals between consecutive cocaine infusions, and (6) are most evident at lower to intermediate cocaine doses. These results suggest that social stress effectively activates the motor routines that are involved in cocaine-seeking rather than increasing the drug's reinforcing efficacy.

Analysis of Variance↗
PubMed1996

Stress induced disorganization of circadian and ultradian rhythms: comparisons of effects of surgery and social stress.

Persistent autonomic disturbances following stressful events suggest that the rhythmical nature of homeostatic functioning may be disrupted by these experiences. We assessed the effects of two different stressors on circadian and ultradian rhythms of Long-Evans rats by using nonlinear multi-oscillator cosinor analysis. Heart rate and intraperitoneal temperature were monitored continuously in 5-min intervals in two groups of animals via radio-telemetry for 15 days after surgery (n = 9) and 15 days following social defeat (n = 6). Circadian amplitude of heart rate and temperature increased significantly for the first nine days of the recovery from surgery but only circadian temperature amplitude increased following social defeat. Circadian acrophase of temperature but not heart rate changed significantly for a similar period following the surgery but not after the social defeat. A mathematical model incorporating the first five harmonics of the circadian rhythm was found to fit the data significantly better than a circadian model alone with rhythms of 3 and 5 cycles/day in temperature and heart rate entraining significantly to the light-dark schedule. Full recovery of the circadian and ultradian rhythms did not occur until a minimum of nine to twelve days after surgery or social defeat. The results suggest that rhythms with multiple periodicities are involved in homeostatic functioning and that models incorporating these rhythms may aid in understanding an organisms adaptive response to surgical intervention and social defeat, long after the challenges have terminated.

Activity Cycles↗
PubMed1996

Primate vocalizations during social separation and aggression: effects of alcohol and benzodiazepines.

The most common group of squirrel monkey vocalizations, peeps, are emitted during different social situations including social separation, affiliative interactions, feeding and aggressive confrontations. The present experiments investigated whether peeps and other vocalizations emitted during different social contexts are pharmacologically altered in a similar manner. First, vocalizations were characterized during (1) social separation in juveniles, and (2) "resident-intruder" aggressive confrontations between dominant monkeys from different social groups. Then, the effects of alcohol (EtOH) and the benzodiazepine chlordiazepoxide (CDP) on vocalizations during social separation and during aggression were examined. Isolated juveniles emitted only one type of call, the isolation peep. Resident monkeys primarily emitted peeps, but also emitted cackles, chucks, noisy calls and pulsed calls. Aggressive peeps were similar in structure and frequency (kHz) to isolation peeps, but were shorter in duration. At the same doses, both CDP (0.3-3 mg/kg) and EtOH (0.1-1.0 g/kg) reduced explosive motor behaviors and isolation peeps in juvenile monkeys during social separation and increased threat displays and aggression peeps in resident monkeys during confrontations with an intruder monkey from a different social group. Thus, similarly structured vocalizations that were emitted during social separation and aggression were very sensitive to EtOH and CDP, but the social context determined the direction and magnitude of effects.

Aggression↗
PubMed1995

Aggression, anxiety and vocalizations in animals: GABAA and 5-HT anxiolytics.

A continuing challenge for preclinical research on anxiolytic drugs is to capture the affective dimension that characterizes anxiety and aggression, either in their adaptive forms or when they become of clinical concern. Experimental protocols for the preclinical study of anxiolytic drugs typically involve the suppression of conditioned or unconditioned social and exploratory behavior (e.g., punished drinking or social interactions) and demonstrate the reversal of this behavioral suppression by drugs acting on the benzodiazepine-GABAA complex. Less frequently, aversive events engender increases in conditioned or unconditioned behavior that are reversed by anxiolytic drugs (e.g., fear-potentiated startle). More recently, putative anxiolytics which target 5-HT receptor subtypes produced effects in these traditional protocols that often are not systematic and robust. We propose ethological studies of vocal expressions in rodents and primates during social confrontations, separation from social companions, or exposure to aversive environmental events as promising sources of information on the affective features of behavior. This approach focuses on vocal and other display behavior with clear functional validity and homology. Drugs with anxiolytic effects that act on the benzodiazepine-GABAA receptor complex and on 5-HT1A receptors systematically and potently alter specific vocalizations in rodents and primates in a pharmacologically reversible manner; the specificity of these effects on vocalizations is evident due to the effectiveness of low doses that do not compromise other physiological and behavioral processes. Antagonists at the benzodiazepine receptor reverse the effects of full agonists on vocalizations, particularly when these occur in threatening, startling and distressing contexts. With the development of antagonists at 5-HT receptor subtypes, it can be anticipated that similar receptor-specificity can be established for the effects of 5-HT anxiolytics.

Aggression↗
PubMed1995

Alcohol, anxiolytics and social stress in rats.

The main objective was to compare the anxiolytic-like profiles of alcohol, diazepam and gepirone along the stress intensity gradient which characterizes consecutive phases of a social confrontation. The acute social stress situation consisted of initially placing the experimental rat as an intruder into the homecage of a resident while the resident was not present, termed the "anticipatory" phase, thereafter permitting brief physical agonistic interactions with the re-introduced resident until the intruder was forced into a submissive supine posture and emitted ultrasonic vocalizations (USV), and eventually exposing the intruder to the resident's threats for 1 h, while being shielded from potential injurious attacks. The hyperthermia, measured via telemetry, in the "anticipatory" phase prior to defeat and in reaction to threats, was decreased by alcohol, gepirone and diazepam; alcohol and gepirone were also effective in attenuating "anticipatory" tachycardia. Alcohol, like gepirone and diazepam, also decreased defensive responses and ultrasonic vocalizations in the "anticipatory" phase of the confrontation, but none of these drugs affected defensive reactions to threats which immediately followed defeat. Gepirone had no systematic sedative effects throughout the confrontation; infact, it dose-dependently reduced the stress-induced suppression of locomotor activity during the "anticipatory" phase. In contrast, at higher doses, alcohol as well as diazepam had marked sedative effects as evidenced by several behavioral parameters (i.e. lie, crouch, walk). The anxiolytic-like profile of hyperthermia, tachycardia, USV and defensive behavior in the "anticipatory" phase of the confrontation by alcohol, gepirone and diazepam contrasted with the lack thereof during the more intense reactive phase. This differential pattern of effects appears to be relevant to the clinical distinctions between anticipatory anxiety and other affective disturbances.

Animals↗
PubMed1995

Delta opioid receptors: reflexive, defensive and vocal affective responses in female rats.

Ultrasonic vocalizations may be an expression of the affective pain response in laboratory animals. The present experiment compares the effects of morphine to the delta agonist, DPDPE (D-Pen2,D-Pen5 enkephalin) on a range of reflexive, behavioral and affective responses during an aggressive interaction. In experiment 1, naive female Long-Evans rats received morphine (0, 1, 3, 6, 10 micrograms ICV), or DPDPE (0, 30, 60, 100 micrograms ICV). In experiment 2, female rats were treated with naltrindole (1.0 mg/kg IP) 20 min before DPDPE (0, 60, 100 micrograms ICV). The following endpoints were measured: (1) latency to tail flick in response to heat stimuli; (2) high (33-65 kHz) and low (20-32 kHz) frequency ultrasonic and audible vocalizations; (3) defensive behavior; and (4) motoric activity. Following a brief exposure to attack, rats were threatened by the aggressor but protected from further attack by a large, wire mesh cage, thereby allowing for continued behavioral and vocal measurement without the risk of physical injury; video and audio recordings were made during the attack and then during a portion of the protected encounter (2 min). Morphine suppressed pain reactions varying in complexity from a spinal reflex, to an organized escape reaction, to an affective vocal response. The delta agonist, DPDPE, attenuated high frequency ultrasonic calling and tail flick responding. Defensive behaviors were also modulated by DPDPE at doses that had no effect on walking or rearing, indicating behavioral specificity. By contrast, doses of morphine that decreased defensive upright and escape also decreased motor activity. In female rats, morphine and DPDPE share a common profile of effects on a range of functional end-points, but DPDPE appears to modulate more selectively the reactions related to aversiveness without exerting sedative effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗