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Oral gavage is a popular route of drug administration during preclinical testing. Despite the growing body of information regarding the effects of oral gavage and the stress associated with this technique, the consequences of such exposure during pregnancy or lactation have rarely been investigated. Therefore, we sought to determine the consequences of oral gavage exposure during pregnancy and lactation on the neurodevelopment and behavior of rat offspring. Pregnant Sprague-Dawley dams underwent either no treatment or oral gavage of distilled water once daily from gestational day 7 until postnatal day 21. Oral gavage treatment had no significant effect on maternal parameters, including bodyweight gain, duration of gestation, litter size, and incidence of neonatal death. Compared with their counterparts from untreated dams, male and female progeny of gavaged dams had longer body lengths on PND 7 and 14 but reduced forelimb grip performance on PND 14 and 17. Therefore, the use of oral gavage during pregnancy and lactation in rats can have opposite effects on the somatic and behavioral development of the offspring. These factors should be considered when using oral gavage as a route of administration during pregnancy. In addition, the inclusion of no-treatment controls is important because they may reveal various restraint-associated effects.

Many preclinical studies have aimed to elucidate the effects of methamphetamine (MA) exposure during pregnancy on the offspring in recent years. However, the severity of effects on the neonate may be related to the subcutaneous (sc) route of administration of the drug that is often employed (88% of preclinical studies) and consequently the delivered dose that the foetus is exposed to. To date there is a paucity of comparative studies investigating different routes of administration for MA during pregnancy and it is not known how these different routes compare when it comes to neonatal outcome. Thus, the aim of this study was to determine if the route of administration of MA (oral gavage or sc injection) during pregnancy at a pharmacological dose affects the magnitude of neurodevelopmental and behavioural effects in the resultant rat offspring. Pregnant Sprague-Dawley dams (n=10 dams/group) received MA (3.75 mg/kg) or control (distilled water) via oral gavage or sc injection from gestation day 7-21. A range of well-recognised neurodevelopmental parameters were examined in the offspring. When administered sc, MA significantly reduced maternal weight gain and altered maternal behaviour; mothers spent less time in the nest with pups and spent less time nursing compared to controls. Significant impairments in neurodevelopmental parameters were evident in both MA treatment groups. Somatic development such as pinna unfolding, fur appearance and eye opening were all delayed after MA exposure but these impairments were more pronounced in the MA sc group. Other somatic parameters such as ano-genital distance and body length were only impeded by sc MA. Behavioural development in the surface righting, inclined plane and forelimb grip tests were also altered for both MA treatment groups. This study demonstrates that prenatal MA can have a profound effect on neonatal outcome, but this can be exacerbated if given via the subcutaneous route, as well as producing additional effects not seen with the oral gavage route. Consequently, the route of administration should be considered when interpreting preclinical studies investigating prenatal MA exposure., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Methamphetamine (MA) has become a popular drug of abuse in recent years not only in the general population but also amongst pregnant women. Although there is a growing body of preclinical investigations of MA exposure during pregnancy, there has been little investigation of the consequences of such exposure via the breast milk during the neonatal period. Therefore, the aim of this study was to determine the consequences of MA exposure during pregnancy and lactation on neurodevelopment and behaviour in the rat offspring. Pregnant Sprague-Dawley dams received MA (3.75 mg/kg) or control (distilled water) once daily via oral gavage from gestation day 7-21, postnatal day 1-21 or gestation day 7- postnatal day 21. A range of well-recognised neurodevelopmental parameters were examined in the offspring. Prenatal MA significantly reduced maternal weight gain, with a concomitant reduction in food intake. A significant increase in neonatal pup mortality was observed, being most marked in the prenatal/postnatal MA group. Significant impairments in neurodevelopmental parameters were also evident in all MA treatment groups including somatic development (e.g. pinna unfolding, fur appearance, eye opening) and behavioural development (e.g. surface righting, inclined plane test, forelimb grip). In conclusion, this study demonstrates that exposure to MA during any of these exposure periods (prenatal and/or postnatal) can have a profound effect on neonatal outcome, suggesting that regardless of the exposure period MA is associated with detrimental consequences in the offspring. These results indicate that in the clinical scenario, exposure during lactation needs to be considered when assessing the potential harmful effects of MA on offspring development., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

We examined whether blockade of corticotropin-releasing factor (CRF) receptors by a non-peptide CRF antagonist (DMP696) would attenuate the stress hyper-responsiveness that occurs in response to maternal separation. In a social interaction test as well as the elevated plus maze, adult male rats, which had been maternally separated as infants, displayed more anxiety-like behavior compared with handled rats. DMP696 increased social interaction in both groups. In the elevated plus maze however, DMP696 significantly increased open arm time in the maternally separated rats but not in the handled group whereas chlordiazepoxide increased open arm time in both groups. DMP696 also appeared to block stress-induced ACTH secretion more readily in the maternally separated group compared with the handled rats. These observations suggest that CRF antagonists are particularly effective in animals that are hyper-responsive to stress and may therefore have utility in the treatment of anxiety and affective disorders where CRF has been implicated.

Effects of acute and chronic administration of phencyclidine (PCP) on EEG activities and gross behavior were studied in monkeys with electrodes implanted in the brain. Administration of PCP (2.0 or 4.0 mg/kg i.v.) in monkeys produced a biphasic pattern of inhibition and excitation of behavior during 6-8 h observation period. The inhibitory phase appeared 1-3 min after PCP injection, and was uniquely characterized by high-voltage slow waves with delta waves (0.6-0.8 c/sec) in the parietal lobe and by those with theta waves (4-5 c/sec) in the occipital lobe and hippocampus during behavioral stupor. This inhibitory phase lasted 1-1.5 h, and subsequently, high-voltage fast wave with enhancement of theta waves and nystagmus appeared during behavioral arousal. Upon chronic PCP administration, the intensity and duration of the inhibitory phase progressively decreased, while the effects of the excitatory phase increased. The results suggest that PCP administration in monkeys produces a biphasic pattern of inhibitory and excitatory effects and upon chronic administration a tolerance develops to the inhibitory effect while an augmentation of the excitatory effect develops.