Adolescent cannabinoid exposure effects on natural reward seeking and learning in rats.

RATIONALE: Adolescence is characterized by endocannabinoid (ECB)-dependent refinement of neural circuits underlying emotion, learning, and motivation. As a result, adolescent cannabinoid receptor stimulation (ACRS) with phytocannabinoids or synthetic agonists like "Spice" cause robust and persistent changes in both behavior and circuit architecture in rodents, including in reward-related regions like medial prefrontal cortex and nucleus accumbens (NAc). OBJECTIVES AND METHODS: Here, we examine persistent effects of ACRS with the cannabinoid receptor 1/2 specific agonist WIN55-212,2 (WIN; 1.2 mg/kg/day, postnatal day (PD) 30-43), on natural reward-seeking behaviors and ECB system function in adult male Long Evans rats (PD 60+). RESULTS: WIN ACRS increased palatable food intake, and altered attribution of incentive salience to food cues in a sign-/goal-tracking paradigm. ACRS also blunted hunger-induced sucrose intake, and resulted in increased anandamide and oleoylethanolamide levels in NAc after acute food restriction not seen in controls. ACRS did not affect food neophobia or locomotor response to a novel environment, but did increase preference for exploring a novel environment. CONCLUSIONS: These results demonstrate that ACRS causes long-term increases in natural reward-seeking behaviors and ECB system function that persist into adulthood, potentially increasing liability to excessive natural reward seeking later in life.

Sex-specific effects of early life stress on social interaction and prefrontal cortex dendritic morphology in young rats.

Early life stress has been linked to depression, anxiety, and behavior disorders in adolescence and adulthood. The medial prefrontal cortex (mPFC) is implicated in stress-related psychopathology, is a target for stress hormones, and mediates social behavior. The present study investigated sex differences in early-life stress effects on juvenile social interaction and adolescent mPFC dendritic morphology in rats using a maternal separation (MS) paradigm. Half of the rat pups of each sex were separated from their mother for 4h a day between postnatal days 2 and 21, while the other half remained with their mother in the animal facilities and were exposed to minimal handling. At postnatal day 25 (P25; juvenility), rats underwent a social interaction test with an age and sex matched conspecific. Distance from conspecific, approach and avoidance behaviors, nose-to-nose contacts, and general locomotion were measured. Rats were euthanized at postnatal day 40 (P40; adolescence), and randomly selected infralimbic pyramidal neurons were filled with Lucifer yellow using iontophoretic microinjections, imaged in 3D, and then analyzed for dendritic arborization, spine density, and spine morphology. Early-life stress increased the latency to make nose-to-nose contact at P25 in females but not males. At P40, early-life stress increased infralimbic apical dendritic branch number and length and decreased thin spine density in stressed female rats. These results indicate that MS during the postnatal period influenced juvenile social behavior and mPFC dendritic arborization in a sex-specific manner.

Chronic stress alters neural activity in medial prefrontal cortex during retrieval of extinction.

Chronic restraint stress produces morphological changes in medial prefrontal cortex and disrupts a prefrontally mediated behavior, retrieval of extinction. To assess potential physiological correlates of these alterations, we compared neural activity in infralimbic and prelimbic cortex of unstressed versus stressed rats during fear conditioning and extinction. After implantation of microwire bundles into infralimbic or prelimbic cortex, rats were either unstressed or stressed via placement in a plastic restrainer (3 h/day for 1 week). Rats then underwent fear conditioning and extinction while activity of neurons in infralimbic or prelimbic cortex was recorded. Percent freezing and neural activity were assessed during all phases of training. Chronic stress enhanced freezing during acquisition of conditioned fear, and altered both prelimbic and infralimbic activity during this phase. Stress did not alter initial extinction or conditioned stimulus (CS)-related activity during this phase. However, stress impaired retrieval of extinction assessed 24 h later, and this was accompanied by alterations in neuronal activity in both prelimbic and infralimbic cortex. In prelimbic cortex, unstressed rats showed decreased activity in response to CS presentation, whereas stressed rats showed no change. In infralimbic cortex, neurons in unstressed rats exhibited increased firing in response to the CS, whereas stressed rats showed no increase in infralimbic firing during the tone. Finally, CS-related firing in infralimbic but not prelimbic cortex was correlated with extinction retrieval. Thus, the stress-induced alteration of neuronal activity in infralimbic cortex may be responsible for the stress-induced deficit in retrieval of extinction.

British Hyperbaric Association carbon monoxide database, 1993-96.

OBJECTIVES: To study the referral pattern of patients, poisoned with carbon monoxide and subsequently transferred to British hyperbaric oxygen facilities, from April 1993 until March 1996 inclusive. METHODS: A standard dataset was used by hyperbaric facilities within the British Hyperbaric Association. The data on each patient were sent in confidence to the Hyperbaric Unit at Whipps Cross Hospital for analysis. The epidemiology of poisoning and the population studied were analysed. Times of removal from exposure, referral to a hyperbaric facility, arrival at the hyperbaric facility, and start of treatment were recorded. Data on the outcome of the episode were documented in one of the contributing facilities. RESULTS: 575 patients exposed to carbon monoxide were reported as being referred to British hyperbaric facilities in the three years, the busiest facilities being in London and Peterborough. The proportions of accidental and non-accidental exposures were 1:1.05. Of the accidental exposures, central heating faults were responsible in 71.5% of cases (n = 206). Smoke inhalation from fires was responsible for a further 13.5% (n = 39). The mean delay to arrival in a hyperbaric oxygen facility was 9 hours and 15 minutes after removal from exposure. Recovery after treatment was sometimes incomplete. CONCLUSIONS: The reported pattern of referral was regionally weighted towards the south east of England. Smoke inhalation victims were often not referred for hyperbaric oxygen treatment. The delay to treatment was multifactorial; and the mean delay was well in excess of six hours. There is room for improvement in the consistency and speed of referral. Treatment schedules require standardisation. A central advice and referral service would be helpful.

Cardiac dysrhythmias, carbon dioxide tensions and blood halothane concentrations during dental anaesthesia.

Ninety-eight in-patients received halothane anaesthesia for dental surgery following intramuscular premedication with papavaretum and hyoscine. All anaesthetics involved tracheal intubation. Fifty patients breathed spontaneously and 48 were artifically ventilated. The incidence of ectopic dysrhythmias during surgery, both ventricular and supraventricular, was significantly higher in the spontaneously breathing group (34.0%) than in the artificially ventilated group (2.1%). Blood halothane concentrations and end-expiratory carbon dioxide tensions during surgery were both significantly higher in the spontaneously breathing group. However, regression analysis of the data failed to identify either factor as solely responsible for the different incidence of cardiac dysrhythmias. It is likely that at least one further factor is involved.

Penetrating tracheal injury in a child.

A case is reported of a 3.5-year-old child with a stab wound in the neck, that penetrated the trachea. A pneumomediastinum was present. The anaesthetic problems are discussed and the child's management outlined.