PTSD is highly comorbid with cocaine use disorder (CUD), and cocaine users with PTSD + CUD are more resistant to treatment. Here we sought to develop a rat model of PTSD + CUD in order to identify the neurobiological changes underlying such comorbidity and screen potential medications for reducing cocaine seeking in the PTSD population. We utilized a predator scent stress model of PTSD, wherein rats received a single exposure to the fox pheromone 2,5-dihydro-2,4,5-trimethylthiazoline (TMT). One week after TMT exposure, stress-susceptible (susceptible), intermediate, and resilient phenotypes were detected and were consistent with behavioral, corticosterone, and gene expression profiles 3 weeks post TMT. We assessed phenotypic differences in cocaine self-administration, extinction, and cue-primed reinstatement. Susceptible rats exhibited deficits in extinction learning and increased cue-primed reinstatement that was not prevented by Ceftriaxone, an antibiotic that consistently attenuates the reinstatement of cocaine seeking. TMT-exposed resilient rats displayed increased mGlu5 gene expression in the amygdala and medial prefrontal cortex and did not display the enhanced cocaine seeking observed in susceptible rats. Combined treatment with the mGlu5 positive allosteric modulator 3-Cyano-N-(1,3-diphenyl-1 H-pyrazol-5-yl)benzamide (CDPPB), fear extinction, and ceftriaxone prevented the reinstatement of cocaine seeking in susceptible rats with fear extinction an important mediating condition. These results highlight the need for animal models of PTSD to consider stress-responsivity, as only a subset of trauma-exposed individuals develop PTSD and these individuals likely exhibit distinct neurobiological changes compared with trauma-exposed populations who are resilient to stress. This work further identifies glutamate homeostasis and mGlu5 as a target for treating relapse in comorbid PTSD-cocaine addiction.

The present study tested whether pet dogs have stress-buffering effects for children during a validated laboratory-based protocol, the Trier Social Stress Test for Children (TSST-C). Participants were 101 children aged 7–12 years with their primary caregivers and pet dogs. Children were randomly assigned in the TSST-C to a pet present condition or one of two comparison conditions: parent present or no support figure present. Baseline, response, and recovery indices of perceived stress and cortisol levels were computed based on children’s self-reported feelings of stress and salivary cortisol. Results indicated that in the alone (no social support) condition, children showed the expected rise for both perceived stress and cortisol response to stress. Pet dog presence significantly buffered the perceived stress response in comparison to children in the alone and parent present conditions. No main condition effect was observed for cortisol; however, for children experiencing the stressor with their pet present, lower cortisol response to stress was associated with more child-initiated petting and less dog proximity-seeking behavior. The results support the notion that pet dogs can provide socio-emotional benefits for children via stress buffering.

Rationale: Bulimia Nervosa (BN) is highly comorbid with substance abuse and shares common phenotypic and genetic predispositions with drug addiction. Although treatments for the two disorders are similar, controversy remains about whether BN should be classified as addiction. Objectives: Here we review the animal and human literature with the goal of assessing whether BN and drug addiction share a common neurobiology. Results: Similar neurobiological features are present following administration of drugs and bingeing on palatable food, especially sugar. Specifically, both disorders involve increases in extracellular dopamine (DA), D1 binding, D3 mRNA, and ΔFosB in the nucleus accumbens (NAc). Animal models of BN reveal increases in ventral tegmental area (VTA) DA and enzymes involved in DA synthesis that resemble changes observed after exposure to addictive drugs. Additionally, alterations in the expression of glutamate receptors and prefrontal cortex activity present in human BN or following sugar bingeing in animals are comparable to the effects of addictive drugs. The two disorders differ in regards to alterations in NAc D2 binding, VTA DAT mRNA expression, and the efficacy of drugs targeting glutamate to treat these disorders. Conclusions: Although additional empirical studies are necessary, the synthesis of the two bodies of research presented here suggests that BN shares many neurobiological features with drug addiction. While few FDA-approved options currently exist for the treatment of drug addiction, pharmacotherapies developed in the future which target the glutamate, DA, and opioid systems may be beneficial for the treatment of both BN and drug addiction.

Neurobiological mechanisms underlying comorbid posttraumatic stress disorder (PTSD) and cocaine use disorder (CUD) are unknown. We aimed to develop an animal model of PTSD + CUD to examine the neurobiology underlying cocaine-seeking in the presence of PTSD comorbidity. Rats were exposed to cat urine once for 10-minutes and tested for anxiety-like behaviors one week later. Subsequently, rats underwent long-access (LgA) cocaine self-administration and extinction training. Rats were re-exposed to the trauma context and then immediately tested for cue-primed reinstatement of cocaine-seeking. Plasma and brains were collected afterwards for corticosterone assays and real-time qPCR analysis. Urine-exposed (UE; n = 23) and controls not exposed to urine (Ctrl; n = 11) did not differ in elevated plus maze behavior, but UE rats displayed significantly reduced habituation of the acoustic startle response (ASR) relative to Ctrl rats. A median split of ASR habituation scores was used to classify stress-responsive rats. UE rats (n = 10) self-administered more cocaine on Day 1 of LgA than control rats (Ctrl + Coc; n = 8). Re-exposure to the trauma context prevented cocaine reinstatement only in stress-responsive rats. Ctrl + Coc rats had lower plasma corticosterone concentrations than Ctrls, and decreased gene expression of corticotropin releasing hormone (CRH) and Glcci1 in the hippocampus. Rats that self-administered cocaine displayed greater CRH expression in the amygdala that was independent of urine exposure. While we did not find that cat urine exposure induced a PTSD-like phenotype in our rats, the present study underscores the need to separate stressed rats into cohorts based on anxiety-like behavior in order to study individual vulnerability to PTSD + CUD.

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