In a Rat Model of Opioid Maintenance, the G Protein-Biased Mu Opioid Receptor Agonist TRV130 Decreases Relapse to Oxycodone Seeking and Taking and Prevents Oxycodone-Induced Brain Hypoxia.

Background: Maintenance treatment with opioid agonists (buprenorphine, methadone) is effective for opioid addiction but does not eliminate opioid use in all patients. We modeled maintenance treatment in rats that self-administered the prescription opioid oxycodone. The maintenance medication was either buprenorphine or the G protein-biased mu opioid receptor agonist TRV130.

The Role of Peripheral Opioid Receptors in Triggering Heroin-induced Brain Hypoxia.

While it is known that opioid receptors (ORs) are densely expressed in both the brain and periphery, it is widely accepted that hypoxic effects of opioids result solely from their direct action in the CNS. To examine the role of peripheral ORs in triggering brain hypoxia, we used oxygen sensors in freely moving rats to examine how naloxone-HCl and naloxone-methiodide, the latter which is commonly believed to be peripherally restricted, affect brain oxygen responses induced by intravenous heroin at low, human-relevant doses. Similar to naloxone-HCl, naloxone-methiodide at a relatively low dose (2 mg/kg) fully blocked heroin-induced decreases in brain oxygen levels.

Sex differences in anxiety-like behaviors in rats.

The use of animal models for behavioral and pharmaceutical testing is employed in many different fields of research but often relies solely on male animals. When females are included, the existing literature frequently offers inconsistent results regarding the effects of sex and/or estrous cycle on anxiety-like behaviors. Our current study sought to establish baseline or normative behaviors in three commonly employed tests of anxiety-like behavior, and determine any sex or cycle differences.

Interactions of benzodiazepines with heroin: Respiratory depression, temperature effects, and behavior.

Benzodiazepines are important therapeutic drugs, but they are often abused and co-abused with opioids. Clinical evidence suggests that benzodiazepines can inhibit respiration, and when combined with the respiratory-depressive effects of opioids, may increase likelihood of death. In this study we used oxygen sensors coupled with high-speed amperometry and multi-site thermorecording to examine how intravenous (iv) midazolam, a potent benzodiazepine, modulates the brain hypoxic and temperature effects of iv heroin in freely-moving rats.

Opposing mechanisms underlying differential changes in brain oxygen and temperature induced by intravenous morphine.

Morphine remains widely used in clinical settings due to its potent analgesic properties. However, one of the gravest risks of all opioids is their ability to induce respiratory depression and subsequent brain hypoxia that can lead to coma and death. Due to these life-threatening effects, our goal was to examine the effects of intravenous morphine at a wide range of doses (0.

Intravenous Cocaine Increases Oxygen Entry into Brain Tissue: Critical Role of Peripheral Drug Actions.

Although it is well established that the direct action of cocaine on centrally located neural substrates is essential in mediating its reinforcing properties, cocaine induces very rapid immediate neural effects that imply cocaine's action on peripheral neural substrates. We employed oxygen sensors coupled with high-speed amperometery to examine the effects of standard cocaine HCl that easily enters the blood-brain barrier and its blood-brain barrier-impermeable methiodide analogue on oxygen levels in the nucleus accumbens in awake, freely moving rats. Both drugs induced strong increases in nucleus accumbens oxygen levels, which displayed similarly short, second-scale latencies and a general similarity with oxygen increases induced by an auditory stimulus.

Changes in brain oxygen and glucose induced by oxycodone: Relationships with brain temperature and peripheral vascular tone.

Oxycodone is a semi-synthetic opioid drug that is used to alleviate acute and chronic pain. However, oxycodone is often abused and, when taken at high doses, can induce powerful CNS depression that manifests in respiratory abnormalities, hypotension, coma, and death. Here, we employed several techniques to examine the effects of intravenous oxycodone at a wide range of doses on various metabolism-related parameters in awake, freely-moving rats.