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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. Then, they were administered repeatedly with saline, hydrocodone, or morphine (20 mg/kg for 5 days, and then 40 mg/kg for 5 days). Subsequently, they were examined for the expression of locomotor sensitization and retested for the effects of opioids on their sociability, anxiety levels, and pain sensitivity. On the basis of their baseline sociability level, mice were divided into socially avoiding and socially exploring. Socially avoiding and socially exploring mice did not differ in their baseline weight and anxiety sensitivities. Socially avoiding mice had slightly higher baseline heat sensitivity than those in socially exploring mice. Repeated administration of opioids had differential effects in socially avoiding and socially exploring mice. In both social groups, repeated morphine administration had overall stronger effects compared with hydrocodone. Morphine-treated socially exploring mice developed greater locomotor sensitization than those in morphine-treated socially avoiding mice. Morphine-treated socially avoiding mice, but not socially exploring mice, spent more time in the center zone of the open-field test and in the light zone of light/dark boxes, and developed heat hyperalgesia. This study suggests that socially exploring animals are more sensitive to the sensitizing effects of opioids. In contrast, opioids have greater effects on the stress and pain systems of socially avoiding animals. Thus, the underlying mechanisms for developing OUD might differ in individuals with various sociability levels.

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. Blocking the sensation of social grooming in morphine-treated mice housed with drug-naive mice (i.e. morphine cage mates) significantly increased the display of jumping behavior in morphine-withdrawn animals. Activating the sensation of social grooming in morphine-treated animals housed solely with other morphine-treated animals (i.e. morphine only) did not significantly alter the display of jumping behavior in morphine-withdrawn animals. Repetitive jumping behaviors have been shown to correlate with morphine dependence. Thus, this study showed a role of social grooming in the protective effect of being housed with drug-naive mice on the development of morphine dependence. It further confirms a role of social support in the development of substance use problems.

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. Then, they were subjected to burn or sham injury to the dorsal surface of the hindpaw and treated orally with morphine, oxycodone, hydrocodone (20 or 40 mg/kg), or saline twice daily throughout the study. They were retested on days 4, 7, 11, 14, 21, and 28 following the burn injury. The antinociceptive effects of the various drugs were analyzed by computing the daily difference between pain sensitivity threshold scores (in g) before and after treatment. This study showed that burn injury decreases opioid antinociception potency. A marked reduction was observed in the antinociceptive effectiveness of all opioids, and for both doses, in the burn-injured versus the sham animals. These results suggest that burn trauma limits the ability of opioids to be effective in reducing pain.

The focus of the present review is the modulation of eating by the endogenous catecholamines (CA) dopamine (DA) and norepinephrine (NE). Topics addressed include pharmacological and genomic manipulations of brain CA systems and subsequent changes in ingestive behavior. DA in particular is a key component of brain reinforcement systems and feeding-associated changes in DA may play a role in the reinforcing aspects of feeding. NE has been linked to both stimulation and suppression of eating and recent evidence has linked these effects to activation of distinct adrenoceptor subtypes. Recent evidence suggests that NE systems may interact with DA systems to augment the activational effects of psychostimulant drugs, such as cocaine or amphetamine, and DA/NE interactions may play a key role in the capacity of psychostimulants to suppress eating.

THE present study examined the effect of pre-exposure to a moderate dose of caffeine (20 mg kg-1) on the acquisition of self-administration of cocaine (0.125 mg kg-1/infusion or 0.25 mg kg-1/infusion) in the rat. Rats pre-exposed to caffeine acquired self-administration more rapidly. Furthermore, sensitization to cocaine's reinforcing effects was accompanied by an increase in the neurochemical response of the mesolimbic dopamine system to an acute injection of cocaine (10 mg kg-1, i.p.) as measured by in-vivomicrodialysis. Thus, the data suggest that exposure to caffeine can increase the reinforcing effects of cocaine, possibly via an enhanced response of the mesolimbic dopamine system.

This unit describes a method for measuring the consumption of a pellet diet during a 30-min testing session conducted during the late portion of the day. The procedure generates reliable and stable baseline measures of feeding, and is appropriate for assessing experimental manipulations that either enhance (e.g., injecting a peptide into the brain) or suppress feeding (e.g., systemic injections of amphetamine).

Some examples of procedures used by feeding researchers are discussed in this unit and include ablation of neural function; inhibition of behaviors by selective neurotoxins and antisense oligonucleotides; staining of sensory and motor mechanisms; electrical stimulation of the brain; local injection and microdialysis of nutrients, neurotransmitters, and drugs; autoradiography and in situ hybridization of neurotransmitters with their receptors; electrophysiological techniques for multi- and single-unit recording of cells in the hypothalamus; and gene technology using inbred strains of genetically obese mice.

The experiment compared the influence of pre-exposure to a .1% saccharin CS on the conditioned taste aversion induced by lithium chloride (.15 M) and by d-amphetamine (2.0 mg/kg) in 44 female Long-Evans hooded rats. Nonpre-exposed rats displayed substantial lithium- and amphetamine-induced taste aversions while pre-exposed rats (6 days) displayed significant attenuation of taste aversion induced by lithium or amphetamine. Although the aversions induced by these reinforcers are anatomically and pharmacologically independent, manipulations of conditioning variables were not sufficient to dissociate these reinforcers.