Erin Jane Campbell

The University of Newcastle, Australia · School of Biomedical Sciences and Pharmacy

Key Clinical Message This case suggests using dual orexin receptor antagonists to treat alcohol use disorder and comorbid sleep disorders may be effective, commencing treatment in withdrawal and continuing it to prevent relapse. Abstract Effective medications for the treatment of alcohol use disorder are limited. This is partially due to the heter...

Impaired motivational drive is a key feature of depression. Chronic stress is a known antecedent to the development of depression in humans and depressive-like states in animals. Whilst there is a clear relationship between stress and motivational drive, the mechanisms underpinning this association remain unclear. One hypothesis is that the endocri...

Maintaining abstinence and preventing relapse are key to the successful recovery from alcohol use disorder. There are two main ways individuals with alcohol use disorder abstain from alcohol use: forced (e.g., incarceration) and voluntary. Voluntary abstinence is often evoked due to the negative consequences associated with excessive alcohol consum...

It is well-established that stress and negative affect trigger eating disorder symptoms and that the brains of men and women respond to stress in different ways. Indeed, women suffer disproportionately from emotional or stress-related eating, as well as associated eating disorders such as binge eating disorder. Nevertheless, our understanding of th...

The nucleus accumbens shell is a critical node in reward circuitry, encoding environments associated with reward. Long-range inputs from the ventral hippocampus (ventral subiculum) to the nucleus accumbens shell have been identified, yet their precise molecular phenotype remains to be determined. Here we used retrograde tracing to identify the vent...

Impaired motivational drive is a key feature of depression. Chronic stress is a known antecedent to the development of depression in humans and depressive-like states in animals. Whilst there is a clear relationship between stress and motivational drive, the mechanisms underpinning this association remain unclear. One hypothesis is that the endocri...

Compulsive overeating of palatable food is thought to underlie some forms of obesity. Similarities are often observed in the behavioural symptomology and the neuropathophysiology underlying substance use disorder and compulsive overeating. As such, preclinical animal models which assess addiction-like behaviour towards food may assist the understan...

MADDERN, X.J. et al., Enhancing the clinical efficacy of cognitive and psychological approaches to treat substance use disorders through mechanism-guided interventions. NEUROSCI BIOBEHAV REV.(.) XXX-XXX, 2022. - Despite decades of research in the field of addiction, relapse rates for substance use disorders remain high. Consequently, there has been...

Projections to the striatum are well-identified. For example, in the ventral striatum, two major inputs to the medial nucleus accumbens shell include the ventral subiculum and basolateral amygdala. However, the chemical phenotype(s) of these projection neurons remain unclear. In this study, we examined amygdalostriatal and corticostriatal connectiv...

Muscarinic acetylcholine receptors (mAChRs) have been shown to mediate alcohol consumption and seeking. Both M4 and M5 mAChRs have been highlighted as potential novel treatment targets for alcohol use disorders (AUD). Similarly, M1 mAChRs are expressed throughout reward circuitry, and their signaling has been implicated in cocaine consumption. Howe...

Persistent alcohol use despite negative consequences is a key feature of alcohol use disorder (AUD) and is typically assessed using punishment in animal models. This study examined relapse-like behavior in male and female alcohol-preferring iP rats following punishment-imposed voluntary abstinence to alcohol seeking. We focused on alcohol seeking i...

Alcohol use disorder (AUD) and methamphetamine use disorder (MUD) are prevalent and have high adverse impacts on both the individual and society. Current treatment strategies for these disorders are ineffective at a population level. Lorcaserin, a 5-HT2C receptor agonist, has shown potential at reducing the symptoms of substance use disorder. This...

Understanding brain structures and circuits impacted by alcohol use disorder is critical for improving our future prevention techniques and treatment options. A brain region that has recently gained traction for its involvement in substance use disorder is the insular cortex. This brain region is multi‐functional and spatially complex, resulting in...

Background The lateral hypothalamic orexin (hypocretin) system has a well-established role in the motivation for reward. This has particular relevance to substance use disorders since orexin-1 receptors play a critical role in alcohol-seeking behavior, acting at multiple nodes in relapse-associated networks. Aims This study aimed to further our un...

Traumatic events during early life have been linked with later life psychopathology. To understand this risk factor, researchers have studied the effects of prenatal and postnatal early life stress on neurochemical changes. Here we review the rodent literature on sex differences and sex‐specific impact of early life stress on frontal cortex neuroch...

The central nucleus of the amygdala (CeA) is a key hub of the neural circuitry regulating alcohol and stress interactions. However, the exact neuronal populations that govern this interaction are not well defined. Here we examined the role of the neuropeptide cocaine and amphetamine regulated transcript (CART) within the CeA in stress-induced alcoh...

Alcohol use disorder (AUD) is a complex neuropsychiatric disease state in which currently approved pharmacotherapeutics are of relatively low effect at a population level. One reason for this may be that current pharmacotherapeutics focus on the reward pathway in relapse prevention, rather than addressing AUD from a holistic perspective. Importantl...

Overeating is a major contributing factor to obesity and related health complications. For women in particular, negative emotions such as stress strongly influence eating behavior and bingeing episodes. Modelling this type of binge eating in rodents presents challenges: firstly, stress‐induced anorexia is commonly observed in rodents therefore a mi...

Environmental enrichment during periods of abstinence can reduce the risk of relapse to drug-seeking behavior. We trained rats to self-administer alcohol in one environment (Context A), then punished their alcohol-reinforced lever responses in a different environment using contingent foot shock (Context B). Rats were then kept in forced abstinence...

Results from clinical studies suggest that drug relapse and craving are often provoked by exposure to drug-associated contexts. Since 2002, this phenomenon has been modeled in laboratory animals using the ABA renewal model. In the classical version of this model, rats with a history of drug self-administration in one context (A) undergo extinction...

Humans with alcohol use disorder typically abstain because of the negative consequences associated with excessive drinking, and exposure to contexts previously associated with alcohol use can trigger relapse. We used a rat model that captures a characteristic of this human condition: namely voluntary abstinence from alcohol use because of contingen...

The neuropeptide oxytocin has been associated with food intake and feeding behaviour. This systematic review aimed to investigate the impact of oxytocin on dietary intake and feeding behaviour in rodent studies. Six electronic databases were searched to identify published studies to April 2018. Preclinical studies in mice and rats were included if...

Corticotropin releasing factor (CRF) is a key component of stress responsivity, modulating related behaviors including anxiety and reward. Difficulties identifying CRF neurons, using traditional approaches including immunohistochemistry, has led to the development of a number of transgenic CRF reporter mice. The Crh-IRES-Cre::Ai14 (tdTomato) report...

There are currently 3 FDA approved treatments for alcohol use disorder (AUD) in the USA, opioid receptor antagonists such as naltrexone, disulfiram and acamprosate. To date, these have been largely inadequate at preventing relapse at a population level and this may be because they only target certain aspects of AUD. Recently, suvorexant, a dual ore...

Alcohol use disorder is a complex syndrome with multiple treatment points including drug-induced pathology, withdrawal management, behavioral/cognitive strategies, and relapse prevention. These different components may be complicated by genotype and phenotype. A huge milestone for the treatment of alcohol use disorder across several countries in th...

Emerging evidence has demonstrated that paternal alcohol use can modify the behavior of offspring, particularly male offspring. However, preclinical studies to date have not used voluntary self-administration of alcohol to examine alcohol-related behaviors in offspring. Here, we tested the hypothesis that paternal alcohol self-administration follow...

Contexts exert bi-directional control over relapse to drug seeking. Contexts associated with drug self-administration promote relapse, whereas contexts associated with the absence of self-administration protect against relapse. The nucleus accumbens shell (AcbSh) is a key brain region determining these roles of context. However, the specific cell t...

The last decade has seen major advances in neuroscience tools allowing us to selectively modulate cellular pathways in freely moving animals. Chemogenetic approaches such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) permit the remote control of neuronal function by systemic drug administration. These approaches have drama...

Altered motivated behaviour is a cardinal feature of several neuropsychiatric conditions including mood disorders. One well-characterized antecedent to the development of mood disorders is exposure to early life stress (ELS). A key brain substrate controlling motivated behaviour is the lateral hypothalamus (LH). Here we examined the effect of ELS o...

Eating is a learned process. Our desires for specific foods arise through experience. Both electrical stimulation and optogenetic studies have shown that increased activity in the lateral hypothalamus (LH) promotes feeding. Current dogma is that these effects reflect a role for LH neurons in the control of the core motivation to feed, and their act...

Individual variations in animal behaviour can be used to describe relationships between different constructs, as well as the underlying neurobiological mechanisms responsible for such variation. In humans, variation in the expression of certain traits contributes to the onset of psychopathologies, such as drug addiction. Addiction is characterised...

In humans, relapse to unhealthy eating habits following dieting is a significant impediment to obesity treatment. Food-associated cues are one of the main triggers of relapse to unhealthy eating during self-imposed abstinence. Here we report a behavioral method examining cue-induced relapse to food seeking following punishment-induced suppression o...

Orexins (hypocretins) are critically involved in coordinating appropriate physiological and behavioral responses to aversive and threatening stimuli. Acute stressors engage orexin neurons via direct projections from stress-sensitive brain regions. Orexin neurons, in turn, facilitate adaptive behavior via reciprocal connections as well as via direct...

Unlabelled: In many human alcoholics, abstinence is self-imposed because of the negative consequences of excessive alcohol use, and relapse is often triggered by exposure to environmental contexts associated with prior alcohol drinking. We recently developed a rat model of this human condition in which we train alcohol-preferring P rats to self-ad...

Exposure to early life physiological stressors, such as infection, is thought to contribute to the onset of psychopathology in adulthood. In animal models, injections of the bacterial immune challenge, lipopolysaccharide (LPS), during the neonatal period has been shown to alter both neuroendocrine function and behavioral pain responses in adulthood...

Chronic pain constitutes a major challenge for clinical and experimental scientists. This is due to the failure of current drugs targeting neurons only. We now know that pain can result from the interaction between the immune, endocrine, and nervous systems. Neonatal LPS exposure can alter neuroendocrine responses in adult rats. How neonatal LPS ex...

Early life physiological stressors have been implicated in the onset of psychopathology in adulthood. In preclinical models, the neonatal bacterial immune challenge, lipopolysaccharide (LPS), has been shown to alter anxiety-like behaviour, neuroendocrine function and behavioural pain responses in adulthood. Interestingly, recent evidence suggests a...

Early life stress (ELS) is a known antecedent for the development of mood disorders such as depression. Orexin neurons drive arousal and motivated behaviors in response to stress. We tested the hypothesis that ELS alters orexin system function and leads to an altered stress-induced behavioral phenotype in adulthood. We also investigated if voluntar...

Animal and human studies have demonstrated that early pain experiences can produce alterations in the nociceptive systems later in life including increased sensitivity to mechanical, thermal, and chemical stimuli. However, less is known about the impact of neonatal immune challenge on future responses to noxious stimuli and the reactivity of neural...

Early life physiological stressors have been implicated in the onset of psychopathology in adulthood. In preclinical models, the neonatal bacterial immune challenge, lipopolysaccharide (LPS), has been shown to alter anxiety-like behaviour, neuroendocrine function and behavioural pain responses in adulthood. Interestingly, recent evidence suggests a...

The tight regulation of sleep/wake states is critical for mental and physiological wellbeing. For example, dysregulation of sleep/wake systems predisposes individuals to metabolic disorders such as obesity and psychiatric problems, including depression. Contributing to this understanding, the last decade has seen significant advances in our appreci...