Dopamine 'ups and downs' in addiction revisited.

Repeated drug use can change dopamine (DA) function in ways that promote the development and persistence of addiction, but in what direction? By one view, drug use blunts DA neurotransmission, producing a hypodopaminergic state that fosters further drug use to overcome a DA deficiency. Another view is that drug use enhances DA neurotransmission, producing a sensitized, hyperdopaminergic reaction to drugs and drug cues. According to this second view, continued drug use is motivated by sensitization of drug 'wanting'. Here we discuss recent evidence supporting the latter view, both from preclinical studies using intermittent cocaine self-administration procedures that mimic human patterns of use and from related human neuroimaging studies. These studies have implications for the modeling of addiction in the laboratory and for treatment.

Nesting material enrichment reduces severity of overgrooming-related self-injury in individually housed rats.

Individual or singly-housing laboratory rats is common in many animal facilities, but has an adverse impact on the welfare of this social species. It has previously been shown that a small proportion of individually housed mice (∼5%) engage in pathological overgrooming behaviour, but this has not been assessed in rats. We performed an observational study to determine the prevalence of overgrooming-related self-injury and whether providing nesting material enrichment throughout an animal's life would affect the prevalence or severity of overgrooming-related self-injury. Due to protocol differences between projects in our behavioural neuroscience lab, unenriched rats received a nylabone and a shelter (n = 167), while baseline-enriched rats received a nylabone, shelter and shredded paper nesting material throughout experiments (n = 238). Unenriched rats received nesting material enrichment after the onset of overgrooming-related self-injury. Over 18 months, rats were monitored by their experimenters on a daily basis (5-7 days/week over 2-3 months/project) and any cases of overgrooming-related self-injury were recorded. Replicating the findings of previous studies in mice, we observed 20 cases of overgrooming-related self-injury (∼5%) with no difference in prevalence between rats on the basis of supplier, cage position, experimental procedure (behavioural only or involving surgical procedures), reinforcer (ethanol or sugar) or level of baseline-enrichment. While there was no difference in onset severity between rats that were unenriched at baseline and baseline-enriched rats, baseline-enriched rats had lower self-injury severity scores at one-, two- and four-week follow-ups. These results suggest that nesting material enrichment provided throughout an animal's life may reduce overgrooming-related self-injury.

Local anaesthetic refinement of pentobarbital euthanasia reduces abdominal writhing without affecting immunohistochemical endpoints in rats.

Sodium pentobarbital is a commonly used agent for euthanizing laboratory rats, however its high pH can cause abdominal discomfort after intraperitoneal injection. Previous studies suggest that the addition of a local anaesthetic may alleviate this discomfort, but the practice has not been widely adopted. We examined the effect of combining lidocaine with pentobarbital on abdominal writhing, defecation, ultrasonic vocalizations, the rat grimace scale and immunohistochemical staining for c-Fos in the nucleus accumbens and basolateral amygdala of the brain. We also compared the amount of abdominal writhing following intraperitoneal administration of pentobarbital-lidocaine with that of pentobarbital-bupivacaine. Our results show that lidocaine reduces abdominal writhing and defecation without affecting immunohistochemistry for c-Fos or latency to loss of posture. However, scores on the rat grimace scale were low in both situations and almost no ultrasonic vocalizations were recorded. Additionally, we found that the amount of abdominal writhing was not significantly different when bupivacaine was used rather than lidocaine. Our results suggest that pentobarbital-induced euthanasia can be refined with the addition of lidocaine or other local anaesthetics.