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K A Miczek

Publications and source records attributed to K A Miczek.

At least 37 records · Page 2Linked to original sources
PubMed2000

Distress vocalizations in maternally separated mouse pups: modulation via 5-HT(1A), 5-HT(1B) and GABA(A) receptors.

RATIONALE: Young rodents emit ultrasonic vocalizations (USVs) when separated from their dams and littermates. Pharmacological agents that act on GABA(A) and/or 5-HT receptors and that alleviate anxiety in humans reduce the emission of these calls. OBJECTIVES: 1) to investigate specific 5-HT1 receptor subtypes that modulate maternal separation-induced USVs in mice; 2) to assess the behavioral specificity of these effects; and 3) to compare 5-HT1 agonists with a positive neurosteroid modulator of the GABA(A) receptor complex. METHODS: Seven-day old CFW mouse pups were isolated from their littermates and placed onto a 20 degrees C surface for 4 min. USVs between 30 and 80 kHz, grid crossing, and rectal temperature were measured in separate groups of mouse pups following subcutaneous administration of 5-HT1A and 5-HT1B receptor agonists and antagonists, the neurosteroid allopregnanolone, or the benzodiazepine midazolam. RESULTS: The 5-HT1A agonists (+)8-OH-DPAT (0.01-0.1 mg/kg) and flesinoxan (0.3-1.0 mg/kg), the selective 5-HT1B agonist CP-94,253 (0.03-30.0 mg/kg), and the mixed 5-HT1B/2C receptor agonist TFMPP (0.1-10.0 mg/kg) dose-dependently reduced USVs. These effects were reversed by the 5-HT1A receptor antagonist WAY 100,635 (0.1 mg/kg) or the 5-HT1B/D receptor antagonist GR 127935 (0.1 mg/kg). The effects of TFMPP were biphasic; low doses (i.e. 0.01 and 0.03 mg/kg) increased the rate of vocalization. Midazolam and allopregnanolone also reduced USVs. The highest doses of flesinoxan, (+)8-OH-DPAT, and allopregnanolone suppressed locomotion, whereas CP-94,253, TFMPP, and midazolam stimulated motor activity. CONCLUSIONS: These experiments confirm that agonists at the 5-HT1 receptors and a positive allosteric modulator of the GABA(A) receptor complex decrease maternal separation-induced USVs in mice, with 5-HT1B manipulations dissociating the effects on vocalizations from sedative effects.

Animals↗
PubMed2000

Cocaine self-administration "binges": transition from behavioral and autonomic regulation toward homeostatic dysregulation in rats.

BACKGROUND: An essential feature of cocaine addiction is the breakdown to control or regulate drug intake. OBJECTIVE: The present studies aimed to examine the transition from regulated intravenous cocaine reinforcement to a more unpredictable, chaotic pattern of cocaine self-administration in rats that were given continuous access to the drug. Autonomic activity was continuously monitored via biotelemetry senders for heart-rate and core temperature before, during and after the cocaine "binges", in an attempt to characterize the breakdown of homeostatic regulation. METHODS: After Long-Evans rats were fitted with intravenous catheters and intraperitoneal telemetry senders, they acquired cocaine self-administration with each fifth lever press being reinforced by a 0.25 mg cocaine infusion. Rats self-administered 15 cocaine infusions daily at stable rates for ca. 2-3 weeks, when continuous access periods ("binges") of 26 and 72 h were scheduled, with a 3-week cocaine-free period between and following the two "binges". RESULTS: A distinctive pattern of cocaine self-administration emerged during the "binges" that consisted of (1) an initial loading phase, (2) stable, predictable inter-infusion intervals for up to 8-10 h, termed "regulatory phase", (3) increased variability in inter-fusion intervals, mostly beginning at 22-24 h of continuous access. During the first half of the 72-h "binge", the autonomic activities remained elevated, showed a greatly constrained variability, and the characteristic circadian rhythmicity was substantially decreased. The average cocaine intake (6.8+/-0.5 mg/kg per hour) during the "regulatory" phase did not change during the subsequent phases. Following the 72-h "binge", the amplitude of autonomic circadian rhythms remained attenuated for more than 2 weeks. In a separate set of animals, the dose effect of inter-infusion intervals following the self-administered infusion was similar during a variable dose protocol, scheduled in an early and a late phase of a 30-h long "binge". CONCLUSIONS: The homeostatic dysregulation during the "binge" as evidenced by the diminished capacity of autonomic functions to vary is accompanied by emerging irregularities in the pattern of cocaine self-administration.

Animals↗
PubMed2000

Reduction of zif268 messenger RNA expression during prolonged withdrawal following "binge" cocaine self-administration in rats.

Cocaine self-administration increases dopamine efflux and neuronal activity in the mesocorticolimbic dopamine system compared with experimenter-administered cocaine. Following a prolonged cocaine self-administration binge, dopamine efflux in the nucleus accumbens is attenuated and behaviors emerge that are indicative of anhedonia and anxiety. The neuronal correlates of these behavioral and neurochemical effects of a cocaine binge were assessed using in situ hybridization histochemistry to detect changes in zif268 messenger RNA expression. Rats were fitted with intravenous catheters; one group was trained to self-administer cocaine (0.5mg/injection), then allowed continuous access to cocaine during a 16h binge, while yoked animals received either saline or cocaine according to the same schedule. Measurement of tactile startle responses and ultrasonic distress calls either immediately after termination of cocaine access or one or 14 days later confirmed peak withdrawal at 24h after the binge. The level of zif268 messenger RNA was lower upon termination of cocaine self-administration than in both yoked treatment groups in the ventral tegmental area and hippocampus. In contrast, zif268 messenger RNA expression increased in the periaqueductal gray matter one day after termination of passive cocaine treatment, coincident with enhanced expression of ultrasonic vocalizations. Zif268 messenger RNA expression decreased over time in the nucleus accumbens core and infralimbic cortex, with reduced expression observed in the nucleus accumbens core, caudatoputamen, hippocampus and amygdala 14 days after termination of cocaine self-administration. The results suggest that withdrawal following a cocaine self-administration binge produces a long-lasting reduction of constitutive zif268 messenger RNA expression in mesocorticolimbic brain regions related to the nucleus accumbens. The relatively greater effect in animals that self-administered cocaine implies a relationship of certain regional responses to behavioral conditioning.

Animals↗
PubMed1999

Social defeat stress increases expression of mu-opioid receptor mRNA in rat ventral tegmental area.

Prompted by previous studies linking social defeat stress to changes in opioid antinociception, we evaluated the expression of mu-opioid receptor (MOR)-encoding mRNA in selected rat brain areas as a function of this type of stress. Because opioids mediate significant regulatory activities of brain dopamine neurons, dopaminergic loci in the ventral tegmental area (VTA) and substantia nigra (SN) were selected for analysis. Within 30 min after social defeat stress, the level of MOR-encoding mRNA, as detected and quantified by in situ hybridization histochemistry, increased in the lateral VTA and this increase was present for at least 6 h. In contrast, defeat stress was without effect on the expression of MOR-encoding mRNA in the SN. These data suggest that stress-induced alteration of MOR-encoding mRNA expression in the VTA may be involved in the consequences of social defeat stress.

Animals↗
PubMed1999

Stress-induced behaviors require the corticotropin-releasing hormone (CRH) receptor, but not CRH.

Corticotropin-releasing hormone (CRH) is a central regulator of the hormonal stress response, causing stimulation of corticotropin and glucocorticoid secretion. CRH is also widely believed to mediate stress-induced behaviors, implying a broader, integrative role for the hormone in the psychological stress response. Mice lacking the CRH gene exhibit normal stress-induced behavior that is specifically blocked by a CRH type 1 receptor antagonist. The other known mammalian ligand for CRH receptors is urocortin. Normal and CRH-deficient mice have an identical distribution of urocortin mRNA, which is confined to the region of the Edinger-Westphal nucleus, and is absent from regions known to mediate stress-related behaviors. Since the Edinger-Westphal nucleus is not known to project to any brain regions believed to play a role in anxiety-like behavior, an entirely different pathway must be postulated for urocortin in the Edinger-Westphal nucleus to mediate these behaviors in CRH-deficient mice. Alternatively, an unidentified CRH-like molecule other than CRH or urocortin, acting through the CRH receptors in brain regions believed to mediate stress-induced behaviors, may mediate the behavioral response to stress, either alone or in concert with CRH.

Animals↗
PubMed1999

Aggression heightened by alcohol or social instigation in mice: reduction by the 5-HT(1B) receptor agonist CP-94,253.

RATIONALE: Models of heightened aggression may be particularly relevant in exploring pharmacological options for the clinical treatment of aggressive and impulsive disorders. OBJECTIVES: To investigate and compare the effects of a 5-HT(1B) selective agonist, CP-94,253, on aggression that was heightened as a result of 1) social instigation or 2) alcohol treatment. METHODS: Male CFW mice were administered 1.0 g/kg EtOH and were subsequently confronted by an intruder in their home cage. In a separate experimental procedure, resident male mice were instigated to aggressive behavior by brief exposure to a provocative stimulus male. To test the hypothesis that activation of the 5-HT(1B )receptor subtype would preferentially attenuate heightened aggression, in comparison to the moderate levels of species-typical aggressive behaviors, the selective agonist, CP-94,253 (1.0-30 mg/kg, IP), and antagonists to the 5-HT(1B) (GR 127935; 10 mg/kg, IP) and the 5-HT(1A) receptor (WAY 100,635; 0.1 mg/kg IP) were used. RESULTS: CP-94,253 suppressed non-heightened aggressive behavior (ED(50)=7.2 mg/kg ). GR 127935, but not WAY 100,635 shifted the ED(50) for CP-94,253 to 14.5 mg/kg. Importantly, the anti-aggressive effects of CP-94,253 were not accompanied by locomotor sedation. Alcohol-heightened and instigation-heightened aggression were suppressed at lower doses than those necessary to suppress non-heightened aggression (ED(50)=3. 8 and 2.7 mg/kg, respectively). CONCLUSIONS: The current results support the hypothesis that activation of 5-HT(1B) receptors modulates very high levels of aggressive behavior in a pharmacologically and behaviorally specific manner.

Aggression↗
PubMed1999

Behavioral sensitization to cocaine after a brief social defeat stress: c-fos expression in the PAG.

The experiments explored the nature and time course of changes in behavior and Fos expression in the periaqueductal grey area (PAG) in response to an injection of cocaine that was given following a single episode of social defeat stress. Social defeat stress was defined as an intruder mouse's response to an aggressive resident mouse. First, the intruder was briefly attacked, and secondly, it was threatened while protected by a perforated cage for 20 min. Plasma corticosterone levels rose after the beginning of the confrontation and remained elevated during the protected phase. In a first experiment, separate groups of intruder and control mice were challenged once with cocaine (20, 30, or 40 mg/kg) or saline. During tests for motor activity, behavioral measurements were obtained via (1) photobeam interruptions, (2) tracking of movements via image analysis, and (3) quantitative ethological analysis of postures and acts via videorecords. Several indices of ambulatory or horizontal forward locomotion confirmed the stimulant effects of cocaine. In a further experiment, separate groups of mice were challenged with 40 mg/kg cocaine at one time point, either during the social stress or 3, 5, 7 or 9 days thereafter. A cocaine challenge significantly increased locomotion 5 and 7 days after a brief social defeat stress, in excess of the level that is seen in non-stressed animals. Further experiments used immunohistochemical assays of sections through the caudal ventrolateral PAG and showed a significant increase in Fos-like immunoreactivity (Fos-LI) 1 h after the social stress experience or after cocaine. Importantly, concurrent administration of cocaine with social defeat stress produced inhibition of Fos expression throughout the PAG. A partial to complete recovery of cocaine-induced Fos expression was observed 5-7 days after social defeat stress. The results suggest that a single social stress episode is sufficient to engender a delayed sensitization of stimulant hyperactivity. The initial inhibition of Fos expression by concurrent social stress and cocaine may point to a relevant initiating event in the process of sensitization to stimulants.

Aggression↗
PubMed1999

Repeated limited access to i.v. cocaine self-administration: conditioned autonomic rhythmicity illustrating "predictive homeostasis".

RATIONALE: Regular cocaine self-administration may act as a "Zeitgeber" in animals and humans, and physiological rhythms may peak at the time when the drug is usually self-administered. OBJECTIVE: To investigate whether or not daily sessions of cocaine self-administration for 2 weeks would synchronize autonomic rhythms to the time of daily access. METHODS: Two weeks after implant of a jugular catheter and telemetry sender, each rat's heart-rate (HR) and core temperature (Tc) rhythms were well entrained to the 12:12-h light:dark cycle (lights off: 0900 hours). For the next 2 weeks rats self-administered cocaine during daily sessions at 1300 hours. The circadian and ultradian oscillations of HR and Tc recorded during the 3 days after the last self-administration (SA) session were quantified by multi-oscillator cosinor analysis. RESULTS: The HR and Tc were elevated during the initial 0.25 mg cocaine infusions of the daily session. This initial tachycardia disappeared as cocaine continued to be self-administered in accumulating amounts, while the locomotor activity remained elevated. After the last SA session the peak (acrophase) of the two cycles/day component in HR and Tc rhythms aligned to the time of day when cocaine self-administration had previously been scheduled. The amplitude of the circadian and ultradian HR and Tc oscillations as well as their circadian acrophase were not impacted by repeated daily time-limited cocaine self-administration. CONCLUSIONS: Cocaine controls the behavior and autonomic functions of rats self-administering limited amounts of cocaine during regular daily sessions, and this controlling influence extends beyond the last daily access period.

Animals↗
PubMed1999

Interactions between social stress and morphine in the periaqueductal gray: effects on affective vocal and reflexive pain responses in rats.

RATIONALE: Endogenous opioid systems within the mesencephalic periaqueductal gray matter (PAG) appear to be intricately involved in many affective, defensive, submissive, and reflexive responses, and these systems are activated by aversive stimuli. OBJECTIVES: The present experiments evaluated the influence of opioid receptors within the PAG on affective vocal and reflexive responses to aversive stimuli in socially inexperienced, as well as defensive and submissive responses in defeated, adult male Long-Evans rats. METHODS: Defeat stress consisted of: (1) an aggressive confrontation with a "resident" stimulus rat in which the experimental "intruder" rat exhibited escape, defensive and submissive behaviors [i.e. upright, supine postures and ultrasonic vocalizations (USV)], and subsequently, (2) protection from the resident rat with a wire mesh screen for ca. 25 min. Defeat stress was immediately followed by an experimental session with thermal antinociceptive and tactile startle stimuli (20 psi airpuffs). RESULTS: The mu opioid receptor agonist morphine (0.3, 1, 3 microgram IC) attenuated startle-induced USV and the tail-flick reflex in socially inexperienced and defeated rats, with both groups of rats demonstrating equal sensitivity to morphine. Morphine decreased defeat-induced USV and increased the display of the crouch posture in defeated rats; these morphine effects in socially inexperienced and defeated rats were re- versed with the opioid receptor antagonist naltrexone (0.1 mg/kg IP). CONCLUSIONS: These results reveal that the ventrolateral PAG is an important site in which mu opioid receptor agonists such as morphine mediate affective vocal and submissive responses, yet this structure is not critical in the display of defeat stress-augmented effects of morphine. Endogenous opioid mechanisms appear to participate in the organization of defensive behavior, namely, to facilitate a shift from active to passive forms of coping.

Aggression↗
PubMed1999

d-amphetamine "cue" generalizes to social defeat stress: behavioral sensitization and attenuated accumbens dopamine.

RATIONALE: Psychomotor stimulant drugs engender intense euphoria as well as anxiogenic effects, both potentially involving the mesolimbic dopamine system. OBJECTIVES: (1) Do animals that discriminate a psychomotor stimulant drug from saline generalize to a non-pharmacological stressful event such as social defeat? (2) How does the generalization from d-amphetamine to social defeat stress relate to dopamine overflow in the mesocorticolimbic system in response to this stress? METHODS: Adult male Long-Evans rats were trained to discriminate either 1.0 mg/kg d-amphetamine or 10 mg/kg cocaine from saline in a two-lever drug discrimination task; each injection-appropriate tenth lever press was reinforced by milk presentation (fixed ratio, FR10). After confirming systematic cocaine and d-amphetamine dose-effect curves, additional discrimination tests involved exposure to several stress conditions; (1) brief confrontations with an aggressive resident rat that resulted in the intruder's defeat. Rats were administered saline, then exposed to aggressive threats behind a protective screen for 15 min, and subsequently performed the two-lever discrimination task; (2) exposure for 15 min to aggressive threats without prior defeat; (3) exposure to a novel cage for 15 min. A subgroup of rats was prepared for in vivo microdialysis after they generalized the social stress response to the d-amphetamine cue. RESULTS: Nine of 35 d-amphetamine-trained and six of 18 cocaine-trained animals responded at least 80% at the drug-appropriate lever after social defeat stress. Social defeat stress increased dopamine in nucleus accumbens, with a closely similar dopamine response in amphetamine-discriminating rats that were behaviorally sensitized versus those that were not sensitized by amphetamine. CONCLUSIONS: Generalization from social stress to the stimulant "cue" differs among individuals, which may be relevant to the anxiety-like effects of stimulants. By contrast, mesolimbic DA activity and motor activity was increased in response to social defeat stress or a d-amphetamine challenge, regardless of the qualitatively different stimulant-stress generalization. Mesolimbic DA in response to stress or amphetamine appears significant in behavioral activation, but not in the qualitatively divergent internal stimulus properties.

Amphetamine↗
PubMed1998

Behavioral sensitization to cocaine after a brief social stress is accompanied by changes in fos expression in the murine brainstem.

The objective of the present study was to determine how c-fos gene expression in brainstem structures after a brief episode of social defeat stress is related to behavioral sensitization to cocaine challenge. Social stress was defined as defeat in a brief confrontation with an aggressive resident mouse and subsequent 20-min exposure to the resident's threats behind a protective screen. Mice were treated with cocaine (40 mg/kg, i.p.) immediately or 1 week after social defeat stress. Fos-like immunoreactive (Fos-LI) cell nuclei were analyzed in the ventral tegmental area (VTA), dorsal raphe nucleus (DR), periaqueductal grey area (PAG) and locus coeruleus (LC). One episode of social stress induced behavioral sensitization to cocaine as indicated by an augmented locomotor response to a challenge injection 7 days after a single defeat. In naive mice, social stress markedly increased the number of Fos-LI nuclei in the DR, PAG and LC, but not in the VTA. Similarly, cocaine administration resulted in a significantly increased number of Fos-LI nuclei in the same areas. Administration of cocaine immediately following social defeat significantly reduced the number of Fos-LI nuclei in the DR, PAG and LC. Cocaine-induced Fos expression returned in the PAG and DR, but not in the LC, 1 week after social stress. In conclusion, the present results suggest that the presence of brainstem Fos be related to the ability to express stress-induced behavioral sensitization to cocaine.

Anesthetics, Local↗
PubMed1998

Withdrawal from i.v. cocaine "binges" in rats: ultrasonic distress calls and startle.

Human cocaine abusers report that they experience intense anxiety during withdrawal from chronic use or "binging". Because the symptoms of cocaine withdrawal are not easily observed, it has been difficult to develop an adequate animal model for cocaine withdrawal that detects anxiety-like behavior. The objective of the present study was to examine the effects of continuous access to i.v. self-administered cocaine on ultrasonic vocalizations (USVs) induced by startling tactile stimuli as a possible animal model for cocaine withdrawal. Five days after implantation of a jugular catheter, rats were placed into self-administration chambers with access to cocaine (0.25 mg/infusion). Once the animal had a stable response rate over 3 days, on a fixed schedule of reinforcement (FR5), they were given unlimited access to cocaine (0.25 mg/infusion) for 48 or 12 h. Subsequently, animals were exposed to 18 air puffs (20 or 10 psi) at 6, 24, 72 h, 7 and 14 days after the "binge". Rats that self-administered cocaine for 48 h and were subsequently startled with 20 psi stimuli increased the number of automatically recorded ultrasonic distress calls and showed an enhanced startle response at 6 h after the last cocaine infusion when compared to handled controls. Animals that self-administered cocaine for 48 h and were subsequently startled with 10 psi stimuli showed increased USVs and an enhanced startle reflex at both 6 and 24 h after the unlimited access. Animals that self-administered cocaine for 12 h also showed an increase in ultrasonic distress calls and enhanced startle responses to 10 psi tactile stimuli when compared to handled controls. USVs during cocaine withdrawal may be interpreted to reflect affective distress during the first 24 h after the last cocaine infusion of 12 or 48 of continuous access to drug.

Animals↗
PubMed1998

Withdrawal from a self-administered or non-contingent cocaine binge: differences in ultrasonic distress vocalizations in rats.

After termination of a self-administered cocaine "binge," rats emit ultrasonic vocalizations (USVs) and these calls may represent affective distress. The present study investigated whether the rates of USVs as indices of withdrawal from a period of continuous access, depends on cocaine being self-administered versus given non-contingently. Five days after implantation of a jugular catheter, triads of rats that were matched for housing, food-training and surgery were placed into experimental chambers. The active rats were allowed to acquire self-administration of cocaine (0.5 mg) while the two yoked animals passively received either cocaine (0.5 mg) or saline according to the active animal's pattern of administration. Once the active animal responded at a stable rate over 3 days, with every third lever press being reinforced by cocaine (FR3), it was allowed free access to cocaine (0.5 mg) for 16 h. Subsequently, all animals were exposed to 18 air puffs (10 psi) at 0, or 1, 3, 5, 7 and 14 days after the "binge". Immediately following the binge, there was no significant difference in the rate of startle-induced USVs between the active cocaine group and the yoked saline group. However, the yoked or non-contingent cocaine rats emitted significantly higher rates of USVs immediately after the last cocaine infusion. At the time of the peak increase in USVs, the active and yoked cocaine groups were significantly different. For up to 5 days after unlimited cocaine access, the active and passive-cocaine groups showed an increase in USVs response when compared to the yoked saline group. The emerging increase in USVs and their gradual decline observed after termination of a cocaine "binge" can be interpreted as an abstinence phenomenon. The non-contingent cocaine appears to be highly aversive, as indicated by the immediate significant increase in the rate of USVs after termination of a cocaine "binge".

Animals↗
PubMed1998

Dissociation of consummatory and vocal components of feeding in squirrel monkeys treated with benzodiazepines and alcohol.

The primary aim of the current experiments was to develop methods that engender vocalizations associated with positive social situations comprising affiliative behavior and feeding that could be quantified under controlled laboratory conditions and were sensitive to anxiolytic drugs. Classical conditioning procedures were used to elicit vocalizations during presentation of stimulus lights (i.e., CS condition) previously paired with either preferred foods (e.g., grapes, peanuts, bananas) or standard foods (e.g., monkey chow) as well as during presentation of both food types (i.e., UCS condition). When compared to the period before stimulus light presentation (i.e., Pre-CS condition), the rate, duration and number of elemental units of food-related "twitter" vocalizations were increased during the CS conditions regardless of food type. Monkeys spent significantly more time oriented toward the food box during the light stimulus that preceded preferred food than for the light stimulus that preceded standard food. However, twitter vocalizations were higher for standard food regardless of the stimulus conditions (i.e., Pre-CS, CS and UCS). Administration of the benzodiazepine full agonist chlordiazepoxide (CDP, 1-10 mg/kg), the partial agonist bretazenil (BRZ, 1-10 mg/kg), the antagonist flumazenil (FLZ, 1-10 mg/kg) and ethyl alcohol (EtOH, 0.1-1.0 g/kg) differentially altered vocalizations. Although CDP and BRZ increased feeding of standard food, twitters were reduced across stimulus conditions. CDP and BRZ did not alter other social contact calls (i.e., "peeps"). FLZ also reduced twitters without altering peeps, but did not increase feeding. In contrast, EtOH did not increase feeding or peeps, but did increase food-related twitters. These results indicate that there is a dissociation between food-related behaviors, such as food consumption and orientation towards the food source, and vocal behaviors associated with group communication during feeding.

Animals↗
PubMed1998

Alcohol-heightened aggression in mice: attenuation by 5-HT1A receptor agonists.

One of the critical mechanisms by which alcohol heightens aggression involves forebrain serotonin (5-HT) systems, possibly via actions on 5-HT1A receptors. The present experiments tested the hypothesis that activating 5-HT1A receptors by selective agonists will block the aggression-heightening effects of ethanol. Initially, the selective antagonist WAY 100635 was used to assess whether or not the changes in aggressive behavior after treatment with 8-OH-DPAT and flesinoxan result from action at the 5-HT1A receptors. Resident male CFW mice engaged in aggressive behavior (i.e. attack bites, sideways threats, tail rattle) during 5-min confrontations with a group-housed intruder male. Quantitative analysis of the behavioral repertoire revealed systematic reductions in all salient elements of aggressive behavior after treatment with 8-OH-DPAT (0.1-0.3 mg/kg, i.p.) or flesinoxan (0.1-1.0 mg/kg, i.p.). The 5-HT1A agonists also reduced motor activities such as walking, rearing and grooming, although to a lesser degree. Pretreatment with the antagonist WAY 100635 (0.1 mg/kg, i.p.) shifted the agonist dose-effect curves for behavioral effects to the right. In a further experiment, oral ethanol (1.0 g/kg, p.o.) increased the frequency of attacks in excess of 2 SD from their mean vehicle level of attacks in 19 out of 76 resident mice. Low doses of 8-OH-DPAT (0.03-0.3 mg/kg) and flesinoxan (0.1, 0.3, 0.6 mg/kg), given before the ethanol treatment, attenuated the alcohol-heightened aggression in a dose-dependent fashion. By contrast, these low 5-HT1A agonist doses affected motor activity in ethanol-treated resident mice to a lesser degree, suggesting behavioral specificity of these anti-aggressive effects. The current results support the hypothesized significant role of 5-HT1A receptors in the aggression-heightening effects of alcohol. If these effects are in fact due to action at somatodendritic 5-HT1A autoreceptors, then the anti-aggressive effects would be associated with decreased 5-HT neurotransmission.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1998

Effects of mu and delta opioid agonists and antagonists on affective vocal and reflexive pain responses during social stress in rats.

The present experiments evaluated the influence of intraventricular mu and delta opioid receptors on affective vocal and reflexive responses to aversive stimuli in socially inexperienced, as well as defensive and submissive responses in defeated, adult male Long-Evans rats. Defeat stress consisted of: (1) an aggressive confrontation in which the experimental intruder rat exhibited escape, defensive and submissive behaviors [i.e., upright, supine postures and ultrasonic vocalizations (USV)], and subsequently, (2) protection from the resident stimulus rat with a wire mesh screen for 10-20 min. Defeat stress was immediately followed by an experimental session with tactile startle (20 psi). The mu opioid receptor agonists morphine (0.1-0.6 microg i.c.v.) and [D-Ala2-N-Me-Phe4-Gly5-ol]-enkephalin (DAMGO; 0.01-0.3 microg i.c.v.), and the delta opioid receptor agonist [D-Pen2,5]-enkephalin (DPDPE; 10-100 microg i.c.v.) dose-dependently decreased startle-induced USV and increased tail-flick latencies in socially inexperienced and defeated rats. Of greater interest, morphine, DAMGO and DPDPE increased the occurrence of the submissive crouch posture, and defeated rats were more sensitive than socially inexperienced rats to the startle-induced USV-suppressive and antinociceptive effects of morphine and DPDPE. The antinociceptive effects of DAMGO were likewise obtained at lower doses in defeated rats. Finally, the USV-suppressive effects of morphine and DAMGO were reversed with the mu receptor antagonist naltrexone (0.1 mg/kg i.p.), but the USV-suppressive effects produced by DPDPE were not reversed with the delta receptor antagonist naltrindole (1 mg/kg i.p.). These results confirm mu, but not delta opioid receptor activation as significant in affective vocal, passive-submissive behavior, as well as reflexive antinociception. Furthermore, similar to previous studies with restraint and electric shock stress, the facilitation of mu opioid effects on vocal responses and antinociception is consistent with the proposal that defeat stress activated endogenous opioid mechanisms.

Aggression↗
PubMed1998

Recurrent aggressive episodes entrain ultradian heart rate and core temperature rhythms.

The present study was designed to investigate the effects of recurrent aggressive episodes on the synchrony of autonomic circadian and ultradian rhythms. Eight aggressive male rats were entrained to a reverse 12 h:12 h light-dark cycle and then implanted with telemetry senders to continuously monitor heart rate (HR) and core temperature (Tc). The amplitude and the time of the peak (acrophase) for each of the circadian and ultradian oscillations were quantified by nonlinear, least-squares, multioscillator cosinor analysis that included the first four harmonics of the circadian rhythm. After recovery from surgery, the 3- and 5-cycle/day ultradian rhythms of HR and Tc were the prominent ultradian components that were synchronized to the light-dark cycle. First, the resident males confronted a male intruder daily at lights-off (0800 hours) for a period of 3 weeks. Second, after a 3-week recovery period, 15 daily aggressive confrontations were scheduled, with the intruders being introduced at 1200 hours. During the course of the confrontations the amplitude of 3- and 5-cycle/day oscillations in HR and Tc decreased, whereas the hemicircadian (2 cycles/day) rhythm amplitude doubled with minor changes of the circadian amplitude. The hemicircadian acrophase coincided with the time of the confrontation most clearly, and this alignment lasted for more than 1 week after the last social confrontation, even in the absence of a reminder. We interpret the synchronization of the hemicircadian acrophases to the time point of social confrontations as anticipating the physiological demands of the aggressive encounters.

Activity Cycles↗