Blocking and sensory preconditioning effects in morphine analgesic tolerance: Support for a pavlovian conditioning model of drug tolerance

Two experiments on rats tested predictions of a Pavlovian conditioning model of drug tolerance which holds that tolerance is the result of compensatory conditioned responses, developed to environmental stimuli accompanying the drug administrations, which attenuate the direct effects of the drug. In Experiment I, the acquisition of tolerance-modulating properties by the tone component of a tone-light compound stimulus which accompanied morphine administrations was reduced by prior light-morphine pairings (blocking). In Experiment II, a tone stimulus acquired tolerance-modulating properties through prior pairings with a light stimulus which later accompanied morphine administrations (sensory preconditioning). These findings are uniquely predicted by the Pavlovian conditioning model of drug tolerance and are incompatible with traditional theories which assign no role to environmental stimuli present at the time of drug administration.     

Organisational effects of neonatal and pubertal testosterone on sexually differentiated behaviours in the open-field and head-dip apparatus

On days 1 and 4 after birth rats were injected with 100 μg of testosterone propionate (TP) or vehicle, and at 35 days of age they were injected intramuscularly with 400 μg of testosterone oenanthate (TO), a long acting androgen, or the vehicle. There were four groups (oil-oil, TP-oil, oil-TO, TP-TO), each group subdivided by sex. Females treated with testosterone neonatally or at puberty were masculinised or defeminised on adult open-field behaviours, being less active and rearing less than oil-oil females; the oil-TO group also defaecated significantly more than controls. The TP-TO female group was indistinguishable from the oil-TO group. In a second experiment, sex differences were found in head-dipping behaviour as well as in activity and rearing. Females treated with TP or TO reared less and defaecated more than controls, and TP also decreased activity, but neither hormone treatment affected head-dipping behaviour. There is thus a peripubertal as well as a neonatal period when testosterone can act organisationally to masculinise or defeminise female rats. Potentiation between effects of neonatal and pubertal androgens was found on female body weights. TO alone had no effect, but TP-TO females were significantly heavier than controls at 90 days of age and by 130 days of age the TP-oil group was also heavier than controls.