Are 50-kHz calls used as play signals in the playful interactions of rats? I. Evidence from the timing and context of their use.

During playful interactions, rats emit increased levels of 50-kHz vocalizations. It is possible that these vocalizations are used as play signals that promote and maintain playful contact. The study investigated this possibility. It was predicted that if these vocalizations are used as play signals, they should be more prevalent (1) before an attack, (2) in attacks leading to wrestling, and (3) in males compared to females, as males play more roughly. Moreover, given that there are at least 15 different subtypes of 50-kHz calls, it is possible that different calls are used in different contexts. Therefore, our prediction (4) was that different subtypes would be used for initiating and terminating playful contact. Pairs of same-sex juveniles were tested so that video recordings of their play and audio recordings of their vocalizations were synchronized. 50-kHz vocalizations occur more often before an attack and in male pairs. Specific calls were associated with specific types of behaviors and these associations differed between male and female rats. However, calls were not more frequent in attacks leading to wrestling than in attacks leading to withdrawal. The data provide qualified support for the hypothesis that 50-kHz vocalizations function as play signals.

Juvenile play experience does not affect nicotine sensitization and voluntary consumption of nicotine in adult rats.

Juvenile play experiences promote behavioral flexibility in rats. If other early positive experiences, such as tactile stimulation, are given prior to exposure to psychostimulants, the behavioral response to the drug is attenuated. The objective of the present study was to determine if the experience of juvenile play behavior would attenuate the response to nicotine. Two experiments were conducted: (1) behavioral sensitization to nicotine exposure, and (2) voluntary consumption of nicotine. For both experiments, rats were reared either with three same-sex peers (play group) or one adult (no play group) during their juvenile period. Then, as adults, half of each group was exposed to repeated injections of nicotine and the other half to saline. Prior play experience had no effect on behavioral sensitization or on voluntary consumption of nicotine. It remains to be determined whether juvenile experience with play influences the rewarding properties of nicotine in social contexts as adults.

Juvenile play experience primes neurons in the medial prefrontal cortex to be more responsive to later experiences.

Juvenile play behavior in rats promotes later behavioral flexibility and appears to do so by modifying the neural systems that regulate the animal's response to unexpected challenges. For example, the experience of play has been shown to prune the dendritic arbor of the cells in the medial prefrontal cortex (mPFC), part of the brain's executive control system. The objective of the present study was to determine if the play-induced changes in the mPFC promotes greater plasticity to experiences later in life. In order to test this possibility, exposure to nicotine was used as the secondary experience given later in life, as it has been shown to produce later changes to the morphology of mPFC pyramidal neurons. Animals were either paired with three same-sex peers (play condition) or one adult (no play condition) during their juvenile period. As young adults, half of the rats from each condition were exposed to repeated injections of nicotine and the other half to injections of saline. The neural plasticity of the mPFC was measured by changes in length and branching of dendrites. Neural changes induced separately by play and by nicotine were consistent with previously published findings. The novel finding was that the cells in the mPFC exhibit a greater response to exposure to nicotine if the rats first had play experience. These findings suggest that juvenile play experiences enhance the plasticity of some neural systems.

CEA and CA 19-9 measurement as a monitoring parameter in metastatic colorectal cancer (CRC) under palliative first-line chemotherapy with weekly 24-hour infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA).

BACKGROUND: There have been contradictory reports on the benefit of CEA and CA 19-9 measurements in patients with metastatic colorectal cancer using palliative chemotherapy. The object of this study was to examine the diagnostic accuracy of monitoring of palliative chemotherapy by means of CEA and CA 19-9. PATIENTS AND METHODS: The tumour markers CEA and CA 19-9 were subjected to serial measurement in patients with metastatic colorectal cancer (n = 90) using palliative first-line chemotherapy with weekly 24-hour infusion of high-dose 5-FU with FA and were compared with objective response according to WHO criteria. 85 patients could be evaluated. 43 patients (51%) initially had elevated CEA (> or = 10 ng/ml) and 33 patients (39%) elevated CA19-9 (> or = 50 IE/ml). In 24 patients (28%), both markers were initially increased. With CEA positive patients, 143 cycles of chemotherapy were carried out, which showed the following response in the various cycles: 21 episodes with progressions (ePD), 69 episodes with no change (eNC), 53 episodes with partial/complete remission (ePR/eCR). With CA 19-9 positive patients, 100 cycles of chemotherapy were carried out with the following results: 21 episodes with progressions (ePD), 48 episodes with eNC, and 31 episodes with ePR/eCR. RESULTS: A CEA rise by at least 50% differentiated between ePD versus eNC/ePR/eCR with a sensitivity of 76% and specificity of 90%. With CEA decreases of at least 30% in 99% of these patient episodes (78 of 79), a tumour progression could be excluded. Patients with an initial drop in CEA after the first cycle of chemotherapy of at least 50% of the initial level had a significantly higher probability of achieving an ePR/eCR in further therapy (relative risk 2.9; P = 0.002). With an CA 19-9 increase of at least 30%, a sensitivity progression of 62% and a specifity of 90% could be calculated. A CA 19-9 decrease of at least 60% excludes a progression in 95% of the patient episodes. CONCLUSIONS: A CEA or CA 19-9 rise is only conditionally appropriate for recording progressions. A progression however, can be excluded with falling levels with high diagnostic accuracy, in which CEA offers a greater degree of certainty than CA 19-9. With a drop in CEA 79 of 143 (= 55%) of the CT scans could be saved, in which case 78 of 79 patient episodes (99%) were correctly assessed as 'no progression'. In patients with an increased CEA and CA 19-9 the CEA determination is sufficient for the further monitoring. A confirmation of these results by multicenter trials can result in a considerable decrease of monitoring costs for palliative treatment.