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In the present study, the effects of morphine exposure in utero on social behavior in juvenile male rats was investigated. Pinning, a measure for play behavior, and social grooming of the offspring were measured at postnatal day 21. The subjects were offspring of Wistar rat dams given sc. injections of 1 or 10 mg/kg body weight morphine HCl daily from gestational days 8 (GD8)-GD 21 and control dams injected daily with saline. Pinning and social grooming of the morphine-treated offspring were significantly elevated compared to saline controls. The doses of morphine used neither affected the gestation of pregnant mother rats nor sensorimotor development of the juvenile rats. Prenatal exposure to morphine of 10 mg/kg daily increased both pinning and social grooming, prenatal exposure to a lower dose of 1 mg/kg increased pinning behavior but not social grooming in the offspring. To study the importance of the gestational period, offspring of dams given 10 mg/kg body weight morphine HCl from GD8-GD15 and saline from GD16-parturition or morphine from GD16-parturition and saline from GD8-GD15 was tested. Pinning was only increased when morphine exposure occurred during the third week of gestation, social grooming was increased when morphine exposure had been in the second week of gestation. Subcutaneous administration of 1 mg/kg naltrexone 1 h before the test significantly decreased play behavior in control rats, but not in animals prenatally exposed to morphine. From these experiments we conclude that the long term effect of in utero exposure to morphine on play behavior is established by affecting the endogenous opioid system.

Changes in analgesia, play behavior, sexual behavior and responsiveness to stress and stimulants have been reported in rodents treated in utero with opiates. During development the endogenous opioids and opioid receptors are present in a tonic balance in the mammalian nervous system. The development of this balance is particularly sensitive to prenatal administration of opioid agonists and antagonists. The motivational and rewarding aspects of play behavior are probably controlled by endogenous opioid systems; low doses of opioids stimulate play behavior, whereas administration of opioid antagonists attenuates play behavior. We have analyzed the effect of morphine administration during the prenatal development of endogenous opioid systems on play behavior in juvenile rats. The doses of morphine used neither affected gestation of pregnant mother rats nor sensorimotor development of the juvenile rats. Levels of social play were elevated in juvenile rats after prenatal exposure to morphine. Social behaviors not related to play and non-social activities were not affected by the prenatal treatment procedure. To study these changes in more detail, social play was investigated using a sequential analysis in prenatally morphine-and saline-exposed pairs. The sequential structure of behavior was not altered by the in utero exposure to morphine. Quantitatively, increases in behavioral transitions were found between behaviors related to play. The prenatal morphine treatment did not affect transitions between behaviors not related to play. It is concluded that the prenatal exposure to morphine did not affect mechanisms underlying play behavior itself, but is probably affecting more general phenomena like reward or motivation to play.

The effects of morphine on social play behavior in juvenile rats were investigated using sequential analysis. Social play behavior of 21-day-old rats treated with 1.0 mg/kg of morphine or saline was analyzed for 15 min. Frequencies and durations of measures of social play behavior, such as pinning, boxing/wrestling and following/chasing were significantly increased after treatment with morphine. Social behaviors not related to play, such as social exploration and crawling over/under were slightly decreased, while social grooming and non-social behavior were not affected by morphine treatment. Using sequential analysis, the dissociation between social behaviors related and unrelated to play was confirmed. Pinning and boxing/wrestling were highly significantly associated. In addition, crawling over/under significantly often preceded social grooming, and an association between social exploration and non-social behavior was found as well. Pinning and boxing/wrestling appeared to be negatively associated with non-social behaviors, social exploration and crawling over/under. A negative association between social grooming and social exploration was also found. Upon treatment with morphine, no major effects on the sequential structure of social behavior were observed: pinning and boxing/wrestling appeared more associated with following/chasing, and the negative association between pinning and boxing/wrestling on the one hand and social exploration on the other was enhanced. Thus, morphine slightly increased the coherence of social play behavior. It is concluded that morphine exerts its effects on social play behavior by increasing social play behavior as a whole rather than by changing its structure, suggesting a key role for opioid systems in the regulation of social play behavior.

To clarify the influence of opioids on social play, the effects of morphine on playful and non-playful social behavior in juvenile rats was investigated under different conditions. Environmental variables employed were different (dim and intense) levels of illumination during testing, familiarity to the test cage, and different periods of social isolation prior to testing. Under dim light conditions, morphine markedly increased playful social behavior, such as pinning, boxing/wrestling and following/chasing, whereas non-playful social behavior such as social exploration and contact behavior was hardly affected. This effect of morphine was independent of duration of previous isolation and dose-dependent, with a maximal effect at 1.0 mg/kg. The mechanism of this effect is interpreted as an action on the rewarding aspects of play. A dose of 0.1 mg/kg of morphine abolished the initial suppression of play induced by unfamiliarity to the test cage, without influencing total levels of play. This may be an effect of morphine on the integration of sensory stimuli. Under intense light conditions, whereas playful behavior was completely suppressed, morphine itself hardly affected such behavior, but decreased some aspects of non-playful social behavior. These results suggest that in juvenile rats playful and non-playful forms of social behavior are differentially regulated. In addition, opioid systems may be involved at different levels in the regulation of social play.

Removal of the pituitary gland in rats leads to suppression of oral morphine and quinine intake behavior. Experiments measuring oral intake of solutions containing graded concentrations of morphine or quinine, revealed that the detection acuity for bitter taste is changed in hypophysectomized (hypox) animals. Treatment of these rats with ACTH 1--24 restored oral morphine intake towards that on intact rats. Morphine consumption in hypox rats was not affected by administration of ACTH 4--10 or ACTH 11--24, but was normalized by treatment with corticosterone. Adrenalectomy also diminished oral morphine intake. It is concluded that hypophysectomized animals refuse a morphine solution because their threshold for bitter taste quality is altered, presumably due to a diminished release of corticosteroids.