Pre-exposure of adolescent mice to morphine results in stronger sensitization and reinstatement of conditioned place preference than pre-exposure to hydrocodone.

Background: Opioids are commonly prescribed to treat moderate-to-severe pain. However, their use can trigger the development of opioid use disorder. A major problem in treating opioid use disorder remains the high rate of relapse.

Response to opioids is dependent on sociability levels.

Social environment influences the trajectory of developing opioid use disorder (OUD). Thus, the present study tested the hypothesis that sociability levels will affect the responses to opioids. Mice were tested for their baseline sociability, anxiety levels, pain sensitivities, and their acute locomotor response to 5 mg/kg opioids.

The role of the vasopressin system and dopamine D1 receptors in the effects of social housing condition on morphine reward.

Background: The association with opioid-abusing individuals or even the perception of opioid abuse by peers are risk factors for the initiation and escalation of abuse. Similarly, we demonstrated that morphine-treated animals housed with only morphine-treated animals (referred to as morphine only) acquire morphine conditioned place-preference (CPP) more readily than morphine-treated animals housed with drug-naïve animals (referred to as morphine cage-mates). However, the molecular mechanisms underlying these effects are still elusive.

The GHR-R antagonist JMV 2959 neither induces malaise nor alters the malaise property of LiCl in the adult male rat.

The orexigenic peptide ghrelin (GHR) interacts with ghrelin receptors (GHR-Rs) to modulate brain reinforcement and feeding circuits. Pharmacological inactivation of GHR-Rs via administration of the drug JMV 2959 attenuates the rewarding/reinforcing effects of several drugs of abuse including alcohol, morphine, amphetamine and nicotine. One view of these results is that inactivation of GHR-Rs taps into brain reinforcement/feeding circuits acted upon by drugs of abuse.

Inhibiting social support from massage-like stroking increases morphine dependence.

Our previous studies showed that altering solely the drug experience of the cage mates with which rodents are housed affects the development of morphine dependence. In this study, we used designer receptors exclusively activated by designer drugs to artificially increase or decrease the activity of peripheral dorsal root ganglia sensory neurons expressing the G-protein-coupled receptor MRGPRB4. This is because sensory MRGPRB4-expressing neurons were shown to specifically detect the sensation of massage-like stroking resulting from social grooming, which is an important affiliative social behavior in the rodent.

Hydrocodone is More Effective than Morphine or Oxycodone in Suppressing the Development of Burn-Induced Mechanical Allodynia.

Background: Pain is the most frequent complaint of burn-injured patients. Opioids are commonly used in the course of treatment. However, there is a lack of rodent studies that examine the differential effects of various opioids on burn pain.

Hydrocodone, but Neither Morphine nor Oxycodone, Is Effective in Suppressing Burn-Induced Mechanical Allodynia in the Uninjured Foot Contralateral to the Burn.

Opioids are commonly used to treat severe, burn-induced pain. However, there is a lack of rodent studies that examine the differential effects of various opioids on burn pain. We recently demonstrated that hydrocodone was superior to other opioids in suppressing the development of burn-induced mechanical allodynia in the burned limb.

Burn injury decreases the antinociceptive effects of opioids.

Burn victim patients are frequently prescribed opioids at doses that are significantly higher than standard analgesic dosing guidelines, and, even despite an escalation in opioid dosing, many continue to experience pain. Thus, the aim of this study was to determine the effect of burn injury on opioid antinociception. Mice were examined for their baseline pain sensitivity thresholds using the von Frey filaments test.

High-fat diet meal patterns during and after continuous nicotine treatment in male rats.

Smoking to control body weight is an obstacle to smoking cessation, particularly in western cultures where diets are often rich in calories derived from fat sources. The purpose of this study was to investigate the effects of continuous nicotine administration on meal patterns in rats fed a high-fat diet. Male rats were housed in cages designed to continuously monitor food intake and implanted with minipumps to deliver approximately 1.

Fluoxetine disrupts motivation and GABAergic signaling in adolescent female hamsters.

Initial antidepressant treatment can paradoxically worsen symptoms in depressed adolescents by undetermined mechanisms. Interestingly, antidepressants modulate GABAA receptors, which mediate paradoxical effects of other therapeutic drugs, particularly in females. Although the neuroanatomic site of action for this paradox is unknown, elevated GABAA receptor signaling in the nucleus accumbens can disrupt motivation.

Differential Effects of Oxycodone, Hydrocodone, and Morphine on Activation Levels of Signaling Molecules.

Background: Opioids alter the responses of D2-like dopamine receptors (D2DRs), known to be involved in the pathology of addiction and other mental illnesses. Importantly, our recent results demonstrated that various opioids differentially modulate the behavioral responses of D2DRs.

Objective: To examine the effect of various opioids on striatal activation levels of Akt and ERK1/2, as well as the signaling responses of D2DRs following opioid exposure.

Sex differences in motivational responses to dietary fat in Syrian hamsters.

Women are more likely than men to exhibit motivational disorders (e.g., anhedonia and anxiety) with limited treatment options, and to overconsume high-fat "comfort foods" to improve motivational disruptions.

Differential effects of oxycodone, hydrocodone, and morphine on the responses of D2/D3 dopamine receptors.

Oxycodone and hydrocodone are opioids which are widely used for pain management and are also commonly misused and abused. The exposure to opioid analgesics has been associated with altered responses of D2-like dopamine receptors (D2DRs). Our recent results suggest that various opioids will differentially modulate the responses of D2DRs.

Social housing conditions influence morphine dependence and the extinction of morphine place preference in adolescent mice.

Background: Adolescent opioid abuse is on the rise, and current treatments are not effective in reducing rates of relapse. Our previous studies demonstrated that social housing conditions alter the acquisition rate of morphine conditioned place preference (CPP) in adolescent mice. Specifically, the acquisition rate of morphine CPP is slower in morphine-treated animals housed with drug-naïve animals.

Ghrelin and ghrelin receptor modulation of psychostimulant action.

Ghrelin (GHR) is an orexigenic gut peptide that modulates multiple homeostatic functions including gastric emptying, anxiety, stress, memory, feeding, and reinforcement. GHR is known to bind and activate growth-hormone secretagogue receptors (termed GHR-Rs). Of interest to our laboratory has been the assessment of the impact of GHR modulation of the locomotor activation and reward/reinforcement properties of psychostimulants such as cocaine and nicotine.

Differential effects of methadone and buprenorphine on the response of D2/D3 dopamine receptors in adolescent mice.

Background: There is a lack of studies that examine the effects of opioid maintenance drugs on the developing adolescent brain, limiting the ability of physicians to conduct a science-based risk assessment on the appropriateness of these treatments for that age group. Our recent observations indicate higher potential risks in repeated exposure to morphine during adolescence, specifically to the D2/D3 dopamine receptors' signaling. Disturbances in dopaminergic signaling could have broader implications for long-term mental health.

Initial characterization of mice null for Lphn3, a gene implicated in ADHD and addiction.

The LPHN3 gene has been associated with both attention deficit-hyperactivity disorder (ADHD) and addiction, suggesting that it may play a role in the etiology of these disorders. Unfortunately, almost nothing is known about the normal functions of this gene, which has hampered understanding of its potential pathogenic role. To begin to characterize such normal functions, we utilized a gene-trap embryonic stem cell line to generate mice mutant for the Lphn3 gene.

Morphine alters the locomotor responses to a D2/D3 dopamine receptor agonist differentially in adolescent and adult mice.

The D2-like dopamine receptors mediate the emotional/aversive state during morphine withdrawal. Given age-dependent differences in the affective responses to withdrawal, this study examined whether the response to dopamine receptor agonists is altered differentially across ages following morphine administration. Adolescent and adult mice were injected with morphine (twice daily, 10-40 mg/kg, s.

Social influences on morphine conditioned place preference in adolescent mice.

Social/peer influences are among the strongest predictors of adolescent drug use. However, this important subject does not get much attention in pre-clinical studies. We recently observed that exposure to different social partners modulates morphine locomotor sensitization.

Analgesia or addiction?: implications for morphine use after spinal cord injury.

Opioid analgesics are among the most effective agents for treatment of moderate to severe pain. However, the use of morphine after a spinal cord injury (SCI) can potentiate the development of paradoxical pain symptoms, and continuous administration can lead to dependence, tolerance, and addiction. Although some studies suggest that the addictive potential of morphine decreases when it is used to treat neuropathic pain, this has not been studied in a SCI model.

Brain reinforcement system function is ghrelin dependent: studies in the rat using pharmacological fMRI and intracranial self-stimulation.

Ghrelin (GHR) is an orexigenic gut peptide that interacts with brain ghrelin receptors (GHR-Rs) to promote food intake. Recent research suggests that GHR acts as a modulator of motivated behavior, suggesting a direct influence of GHR on brain reinforcement circuits. In the present studies, we investigated the role of GHR and GHR-Rs in brain reinforcement function.

Pharmacologic antagonism of ghrelin receptors attenuates development of nicotine induced locomotor sensitization in rats.

Aims: Ghrelin (GHR) is an orexigenic gut peptide that interacts with ghrelin receptors (GHR-Rs) to modulate brain reinforcement circuits. Systemic GHR infusions augment cocaine stimulated locomotion and conditioned place preference (CPP) in rats, whereas genetic or pharmacological ablation of GHR-Rs has been shown to attenuate the acute locomotor-enhancing effects of nicotine, cocaine, amphetamine and alcohol and to blunt the CPP induced by food, alcohol, amphetamine and cocaine in mice. The stimulant nicotine can induce CPP and like amphetamine and cocaine, repeated administration of nicotine induces locomotor sensitization in rats.

Attenuation of cocaine-induced locomotor sensitization in rats sustaining genetic or pharmacologic antagonism of ghrelin receptors.

Systemic infusions of the orexigenic peptide ghrelin (GHR) increase dopamine levels within the nucleus accumbens and augment cocaine-stimulated locomotion and conditioned place preference in rats; observations that suggest an important role for GHR and GHR receptors (GHR-Rs) in drug reinforcement. In the present studies, we examined the development of cocaine locomotor sensitization in rats, sustaining either pharmacologic antagonism or genetic ablation of GHR-Rs. In a pharmacologic study, adult male rats were injected (i.

Social influences on morphine sensitization in adolescent rats.

Given that social influences are among the strongest predictors of adolescents' drug use, this study examines the effects of social interactions on morphine sensitization in both adolescent and adult rats. Rats treated with morphine (twice daily, 6 days, 2.5-10 mg/kg, subcutaneously, s.

Perinatal lead exposure alters locomotion induced by amphetamine analogs in rats.

Aims: The precise neurochemical perturbations through which perinatal (gestation/lactation) lead exposure modifies the reinforcement efficacy of various psychoactive drugs (e.g., cocaine, opiates) are unknown.