naloxone and Anxiety--Separation

The expanded suffocation false alarm theory (SFA) hypothesizes that dysfunction in endogenous opioidergic regulation increases sensitivity to CO2, separation distress and panic attacks. In panic disorder (PD) patients, both spontaneous clinical panics and lactate-induced panics markedly increase tidal volume (TV), whereas normals have a lesser effect, possibly due to their intact endogenous opioid system. We hypothesized that impairing the opioidergic system by naloxone could make normal controls parallel PD patients' response when lactate challenged. Whether actual separations and losses during childhood (childhood parental loss, CPL) affected naloxone-induced respiratory contrasts was explored. Subjective panic-like symptoms were analyzed although pilot work indicated that the subjective aspect of anxious panic was not well modeled by this specific protocol.. Randomized cross-over sequences of intravenous naloxone (2 mg/kg) followed by lactate (10 mg/kg), or saline followed by lactate, were given to 25 volunteers. Respiratory physiology was objectively recorded by the LifeShirt. Subjective symptomatology was also recorded.. Impairment of the endogenous opioid system by naloxone accentuates TV and symptomatic response to lactate. This interaction is substantially lessened by CPL.. Opioidergic dysregulation may underlie respiratory pathophysiology and suffocation sensitivity in PD. Comparing specific anti-panic medications with ineffective anti-panic agents (e.g. propranolol) can test the specificity of the naloxone+lactate model. A screen for putative anti-panic agents and a new pharmacotherapeutic approach are suggested. Heuristically, the experimental unveiling of the endogenous opioid system impairing effects of CPL and separation in normal adults opens a new experimental, investigatory area.

Topics: Adolescent; Adult; Anxiety, Separation; Cross-Over Studies; Female; Humans; Lactic Acid; Male; Middle Aged; Naloxone; Opioid Peptides; Panic Disorder; Respiratory Physiological Phenomena

In adolescent rats, 50-kHz vocalizations are most evident during tickling and rough-and-tumble play. The following experiments evaluated whether 50-kHz vocalizations reflect positive social affect by determining (1) if tickling is a rewarding event, (2) if social or isolate housing conditions differentially influence the response (since housing condition has been found to effect the reward magnitude of social encounters), and (3) if drugs that work on mu-opiate receptors, which has been hypothesized to control positive social affect, modulate tickling. Tickling was positively reinforcing as demonstrated by elevated operant behavior, conditioned place preference, and approach measures. A significant negative correlation between vocalization rate and approach latency measures was found. Social housing reduced tickle-induced vocalizations and approach speeds compared to isolate housing. Naloxone (1 mg/kg) increased vocalization in the socially housed rats and decreased it in isolated Subjects (Ss). These findings suggest that tickling can be used to induce positive social affect in rodents, and that it is modulated by endogenous opioids.

Topics: Animals; Anxiety, Separation; Behavior, Animal; Brain Chemistry; Endorphins; Female; Male; Naloxone; Narcotic Antagonists; Physical Stimulation; Play and Playthings; Rats; Rats, Long-Evans; Receptors, Opioid, mu; Reward; Sexual Behavior, Animal; Social Environment; Vocalization, Animal

Infant rhesus monkeys respond to separation from their mothers with a dramatic increase in vocalizations and activation of autonomic and pituitary-adrenal systems. Using the mother-infant separation paradigm in rhesus monkeys, we focused on the role of opiate systems in modulating the behavioral and neuroendocrine consequences of a brief, naturally occurring stressor. In the first experiment, morphine 0.1 mg/kg significantly decreased separation-induced vocalizations without affecting activity levels. In the second experiment, naloxone 1.0 mg/kg increased distress vocalizations but lower doses had no effect. In the third experiment we blocked the effect of morphine 0.1 mg/kg with naloxone 0.1 mg/kg, a dose of naloxone that had no intrinsic effects of its own. This suggests that the reduction of separation-induced vocalizations by morphine is mediated by opiate receptors. The last experiment demonstrated that separation-induced increases in pituitary-adrenal hormones can also be modulated by opiate agonists and antagonists. These findings are consistent with work in non-primate species and support the hypothesis that opiate receptors are specifically involved in mediating separation-induced vocalizations and pituitary-adrenal activation in primates.

Topics: Animals; Anxiety, Separation; Endorphins; Female; Macaca mulatta; Male; Morphine; Naloxone; Vocalization, Animal

6-day-old mice pups were injected with D-amino acids (D-phenyl-alanine + D-leucine), and their ultrasonic distress vocalizations were measured. D-Amino acids, which exert opioid-like effects, reduce the number of ultrasonic calls without affecting the activity of the pups. This effect is reversed by naloxone, an opioid antagonist. The role of endogenous opioids in modulating early attachment is discussed.

Topics: Animals; Animals, Newborn; Anxiety, Separation; Drug Therapy, Combination; Endorphins; Humans; Leucine; Mice; Naloxone; Object Attachment; Phenylalanine; Ultrasonics; Vocalization, Animal