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Biomedical subjects

M Haney

Publications and source records attributed to M Haney.

At least 55 records · Page 3Linked to original sources

The effects of a monetary alternative on marijuana self-administration.

The availability of alternative reinforcers can reduce drug self-administration. This 21-day residential study investigated the effect of monetary alternatives on marijuana self-administration. Three female and four male participants performed computer tasks (baseline) in the morning before smoking a sample marijuana cigarette (0.0, 1.8, or 3.9% delta 9-tetrahydrocannabinol (THC) and receiving the sample alternative ($5.00 voucher). In the afternoon, participants had five opportunities to choose either the marijuana cigarette sampled earlier or a voucher for $5.00. Participants were required to meet a criterion level of task performance to obtain each choice. The monetary performance criterion varied from day to day (80, 100, or 120% of baseline); the marijuana performance criterion remained constant at 100% of baseline. Choices were delivered in the evening, after task completion. Marijuana choice varied as a function of THC concentration and criterion to earn money. Active marijuana was always chosen more often than placebo, and active and placebo marijuana were chosen over money when the criterion to earn money was high. Task performance improved when criteria were imposed, even after participants had smoked the sample marijuana cigarette. Subjective ratings of drug effects increased with increasing THC concentration, but did not predict choice. The availability of a monetary alternative was effective in shifting choice to self-administer marijuana, and marijuana choice was sensitive to contingency manipulations. The results further indicate that contingency manipulations may override the performance-impairing effects of marijuana observed in other studies.

Adult↗

Binge cocaine self-administration by humans: smoked cocaine.

Tolerance develops to the cardiovascular and subjective effects of intravenous cocaine during single self-administration sessions, but diminishes within 3 h after the session ends. To examine whether a similar pattern of tolerance occurs to smoked cocaine, seven adult 'crack' cocaine users completed a protocol investigating changes in behavior during the repeated self-administration of smoked cocaine. During sessions, participants could self-administer up to 6 doses of smoked cocaine (50 mg per dose), one every 14 min. Both two- and three-day binge conditions were tested. During the two-day binge, a 2.5 h cocaine self-administration session began at 1200 h and again at 1600 h on two consecutive days, while during the three-day binge, self-administration sessions occurred at 1200 h and 1600 h on three consecutive days. The first one or two cocaine doses in each session increased cardiovascular and subjective effects ratings; subsequent cocaine inhalations during the session did not increase these measures further, suggesting the development of acute tolerance to these effects. Ratings of 'I want cocaine' decreased slightly across three days of repeated smoked cocaine self-administration, while anxiety scores increased slightly across three days, suggesting that some effects of smoked cocaine may persist beyond a binge.

Adult↗

Behavioral contingencies modulate alprazolam self-administration by humans.

The effect of monetary contingencies on alprazolam self-administration was evaluated in seven male volunteers living in a residential laboratory. Drug administration occurred prior to an afternoon work session (13.00 h), and at the onset of an evening recreation period (17.30 h). On 'sample' days, participants were administered placebo or alprazolam (0.75 mg), and at the end of the afternoon work session, were told whether their task performance was 'better' or 'worse' than average. If they received 'better' feedback they earned $55, and if they received 'worse' feedback, they earned $15. On 'choice' days, participants chose to self-administer either alprazolam or placebo, with feedback occurring on two of the four choice days. Feedback was not actually linked to performance, but instead was pre-programmed. For one week, alprazolam administration was always associated with 'better' feedback on sample and choice days, and in the other week was associated with 'worse' feedback. When no feedback was delivered, alprazolam was self-administered equally often in the afternoon (57%) and evening (71%). When feedback was delivered, it significantly influenced the choice to self-administer alprazolam in the afternoon. 'Better than average' feedback resulted in alprazolam self-administration 57% of the time, but alprazolam self-administration decreased to 14% when it was associated with 'worse than average' feedback and reduced earnings. A similar pattern of effects has been reported for d-amphetamine. Thus, the self-administration of either a stimulant or a minor tranquilizer is significantly reduced when it is associated with a consequent loss of an alternative reinforcer, in this case money.

Adult↗

Factors influencing marijuana self-administration by humans.

The self-administration of marijuana cigarettes varying in tetrahydrocannabinol (THC) content was measured by having participants choose between marijuana and an alternative reinforcer, i.e., snack food. Twelve marijuana users (eight men, four women), in groups of four, participated in a 16-day residential study. Each day, participants had the opportunity to choose repeatedly between a marijuana cigarette and a snack. The THC concentration of the cigarette changed each day (0.0, 2.2 or 3.9% delta 9-THC w/w), as did the number of snack items (one or two); each THC concentration was compared to each snack condition twice. Days were divided into a work period (09.15-16.45 h), comprising performance and subjective-effects tasks, and a recreation period (17.15-23.30 h). Each day at 10.00 h, participants "sampled" a marijuana cigarette containing the delta 9-THC concentration available that day, and selected the number of snack items available that day. Six "choice" trials occurred from 14.00-19.00 h, when participants responded under a modified progressive ratio schedule for either marijuana or snacks. At 18.15 h, participants could participate in a 10-min math task, in which each correct answer earned $1.00. Cigarettes containing 2.2 or 3.9% delta 9-THC were self-administered more often than placebo. The only other factor influencing marijuana choice was the opportunity to earn additional money, with participants choosing not to smoke immediately before the math task. By the end of the study, active marijuana had smaller effects on ratings of "high", "stimulated," and "good drug effect." These data demonstrate that: (a) delta 9-THC is an essential reinforcing component of marijuana; (b) marijuana use may be manipulated by monetary contingencies; and (c) tolerance may develop more readily to marijuana's subjective effects than its reinforcing effects.

Adult↗

Effect of fluoxetine on food intake of humans living in a residential laboratory.

Ten male and one female normal-weight research volunteers, participating in a 16-day residential study, received oral fluoxetine (40 mg) or placebo at 0930 daily. Food intake, performance and subjective ratings were measured throughout the day. The interaction between fluoxetine and carbohydrate consumption was examined by providing subjects diets that engendered varied levels of carbohydrate intake. When subjects received placebo and had access to a regular diet, they consumed 3400 kcal day-1 (53% carbohydrate, 34% fat, 13% protein); and fluoxetine decreased caloric intake to 2770 Kcal, without affecting macronutrient contribution. Caloric intake (2730 Kcal; 67% carbohydrate) under the high-carbohydrate condition when subjects received fluoxetine was not different from intake under the regular-diet fluoxetine conditions. Subjects reported that the high-fat (low-carbohydrate) diet was less palatable and consumed 2975 Kcal under placebo conditions (35% carbohydrate); fluoxetine decreased caloric intake by an additional 400 Kcal without affecting macronutrient contribution. There was no evidence that carbohydrate intake modulated the effects of fluoxetine. Fluoxetine decreased food intake by decreasing the number of eating occasions. Performance and subjective measures were not significantly altered by fluoxetine compared to placebo. Thus, there was no evidence of a specific effect of fluoxetine on macronutrient consumption, nor were the effects of fluoxetine altered by the macronutrient composition of the available diet.

Adult↗

Amphetamine self-administration by humans: modulation by contingencies associated with task performance.

The effect of task performance feedback and associated monetary earnings on drug self-administration were evaluated using eight subjects in a residential laboratory setting. The hypothesis was that if subjects believed that d-amphetamine impaired performance and reduced monetary earnings, d-amphetamine self-administration would decrease. Subjects performed computer tasks every day: on certain days that they received capsules, subjects were given bogus feedback regarding their performance ("better" or "worse" than average). On sample days, subjects were required to take d-amphetamine (10 mg BID) or placebo (0 mg BID) capsules. On choice days, subjects could choose between either d-amphetamine or placebo. Subjects received feedback on their task performance on 2 sample days and 2 of 4 choice days. Subjects received no feedback on the remaining two choice days. When subjects received no feedback, they chose d-amphetamine over placebo 78% of the time, and when they were given better feedback messages, they chose d-amphetamine 87.5% of the time. In contrast, d-amphetamine self-administration decreased significantly to 25% when subjects were told that it impaired their performance on work tasks and resulted in reduced earnings. In reality, d-amphetamine had little effect on work task performance. However, compared to placebo, d-amphetamine significantly increased subjective ratings of "Stimulated" and "Good Drug Effect" and significantly decreased ratings of "Tired" and "Sleepy." These results demonstrate that d-amphetamine served as a reinforcer under conditions in which drug self-administration did not influence monetary earnings, but that d-amphetamine self-administration could be modified by feedback/monetary earnings. Thus, contingencies associated with performance have important implications for drug use in the workplace.

Adult↗

Effect of fenfluramine on food intake, mood, and performance of humans living in a residential laboratory.

Five male and four female normal weight research volunteers, participating in 13-day residential studies, received oral fenfluramine (20, 40 mg) or placebo at 09:30 and 17:00. Food intake, performance, and subjective ratings were measured throughout the day. Carbohydrate intake was manipulated by providing lunch meals high (males: 120 g; females: 80 g) or low (males: 25 g; females: 16 g) in carbohydrate on 8 days; on the remaining days subjects self-selected lunch. Total caloric intake (approximately 2800 Kcal) did not differ among the low- and high-carbohydrate, and self-selected lunch conditions when subjects received placebo, indicating caloric compensation. Total carbohydrate intake was significantly less, however, when subjects consumed the low-carbohydrate lunch compared to the other lunch conditions. Fenfluramine significantly decreased total caloric intake (approximately 500 kcal) by decreasing meal size, not number, only when subjects consumed the low-carbohydrate lunch. Fenfluramine was only an effective anorectic drug when subjects consumed a lunch with fewer calories and a lower carbohydrate:protein ratio than self-selected baseline. Also, fenfluramine improved performance on a range of computer tasks and increased ratings of "Alert," "Friendly," and "Talkative," while decreasing ratings of "Tired" and "Irritable."

Adult↗

Social stress increases the acquisition of cocaine self-administration in male and female rats.

The effect of social stress on the vulnerability to commence cocaine self-administration was examined in Sprague-Dawley rats repeatedly exposed to aggressive attack by a same-sex opponent. Both sexes were studied, since the factors influencing the acquisition of drug self-administration in females have not been defined. Male and female rats encountered an aggressive male or lactating female opponent on four separate occasions over the course of one week. Control male and female rats were not exposed to attack. All animals were implanted with jugular catheters, and six days later placed into the self-administration box, where a nose-poke in the designated 'active hole' resulted in a 20 microliters injection of cocaine (0.32 mg/kg). Nose-pokes in an 'inactive' hole had no effect. Male and female rats that had experienced social stress self-administered more cocaine than non-defeated controls. The difference between the stressed and non-stressed animals in the number of cocaine injections was not present during the first few days of exposure to cocaine, but became more pronounced over time. Social stress increased the number of responses for cocaine, but did not alter the number of non-specific responses. Sex differences in self-administration were not significant. Therefore, social status appears to be a potent influence in the onset of drug taking behavior in both male and female rats.

Aggression↗

Delta opioid receptors: reflexive, defensive and vocal affective responses in female rats.

Ultrasonic vocalizations may be an expression of the affective pain response in laboratory animals. The present experiment compares the effects of morphine to the delta agonist, DPDPE (D-Pen2,D-Pen5 enkephalin) on a range of reflexive, behavioral and affective responses during an aggressive interaction. In experiment 1, naive female Long-Evans rats received morphine (0, 1, 3, 6, 10 micrograms ICV), or DPDPE (0, 30, 60, 100 micrograms ICV). In experiment 2, female rats were treated with naltrindole (1.0 mg/kg IP) 20 min before DPDPE (0, 60, 100 micrograms ICV). The following endpoints were measured: (1) latency to tail flick in response to heat stimuli; (2) high (33-65 kHz) and low (20-32 kHz) frequency ultrasonic and audible vocalizations; (3) defensive behavior; and (4) motoric activity. Following a brief exposure to attack, rats were threatened by the aggressor but protected from further attack by a large, wire mesh cage, thereby allowing for continued behavioral and vocal measurement without the risk of physical injury; video and audio recordings were made during the attack and then during a portion of the protected encounter (2 min). Morphine suppressed pain reactions varying in complexity from a spinal reflex, to an organized escape reaction, to an affective vocal response. The delta agonist, DPDPE, attenuated high frequency ultrasonic calling and tail flick responding. Defensive behaviors were also modulated by DPDPE at doses that had no effect on walking or rearing, indicating behavioral specificity. By contrast, doses of morphine that decreased defensive upright and escape also decreased motor activity. In female rats, morphine and DPDPE share a common profile of effects on a range of functional end-points, but DPDPE appears to modulate more selectively the reactions related to aversiveness without exerting sedative effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗

Cocaine sensitivity in Roman High and Low Avoidance rats is modulated by sex and gonadal hormone status.

Repeated exposure to stressful stimuli or psychostimulants increases sensitivity to the motoric effects of these drugs, i.e. behavioral sensitization. The objective of the present experiment was to determine the interaction between factors that modulate psychostimulant sensitivity, i.e. sex and circulating gonadal hormone levels, in rats with a genetically distinct locomotor response to novelty: Roman Low Avoidance rats (RLA) freeze while Roman High Avoidance rats (RHA) remain motorically active. Ninety-six male and female RHA and RLA rats were gonadectomized (GDX) just after weaning or as adults, or left gonadally intact. Each rat received a total of 9 injections of cocaine hydrochloride (10 mg/kg, IP), at 3-4 day intervals for 5 weeks. Locomotor activity was measured after each injection, and stereotypes were rated 1 x/week. Open field behavior (10 min) and plasma corticosterone were measured 2 weeks after the final injection. Overall, the RHA line was more sensitive to (1) cocaine's stereotypic effects, and (2) the influence of ovarian hormones on the cocaine's acute and sensitizing effects on locomotor activity. Therefore, genetic background not only determines cocaine sensitivity, but also the influence of gonadal hormones on locomotor activity. These interactions are relevant when considering the genetic contribution to abuse liability.

Animals↗

Psychomotor stimulant effects of d-amphetamine, MDMA and PCP: aggressive and schedule-controlled behavior in mice.

The objective of the present experiments was to characterize psychomotor stimulant effects of d-amphetamine, methylenedioxymethamphetamine (MDMA) and phencyclidine (PCP) on conditioned performance and on aggressive behavior in mice. In a novel protocol with alternating periods of schedule-controlled responding and aggressive behavior toward an intruder it was possible to assess a range of species-specific agonistic acts, postures, and motor activities as well as response rates and patterns engendered by a multiple Fixed Interval (FI) and Fixed Ratio (FR) schedule within the same animal. Initially, it was confirmed that d-amphetamine and, less reliably, MDMA and PCP, increased FI, but not FR responding in mice. In the next experiment, mice confronted an intruder at the midpoint of the 1-h daily session; following the display of aggressive behavior, the rate of FI responding showed an amphetamine-like increase, whereas only a transient change occurred after non-aggressive encounters. Thirdly, using this new protocol, PCP, d-amphetamine and MDMA altered FI and FR responding in a way that was closely similar to the first experiment. Low PCP and d-amphetamine doses increased aggressive behavior erratically in certain individuals, but not reliably for the group. MDMA dose-dependently decreased aggressive behavior, and all drugs disrupted aggressive behavior at higher doses. The characteristic increases in walking and decreases in rearing after higher doses of PCP and d-amphetamine were greatly attenuated when the intruder was present.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗

Ultrasounds emitted by female rats during agonistic interactions: effects of morphine and naltrexone.

Ultrasonic vocalizations may be an expression of the affective pain response in laboratory rodents. The present experiment compared morphine's effects on high (33-60 kHz) and low (20-32 kHz) frequency ultrasonic vocalizations to its effects on a range of unconditioned behavioral responses to aversive stimuli; the influence of estrous cyclicity on morphine sensitivity was also investigated. In experiment 1, naive female Long-Evans rats, selected during estrus or diestrus, received cumulative morphine (1, 3, 6, 10 mg/kg SC) or saline, and in experiment 2, rats were pretreated with naltrexone (0.1 mg/kg IP) 5 min before morphine (17, 30, 60, 100 mg/kg SC). The following endopoints were measured 20-25 min post-injection: (1) tail flick latency; (2) ultrasonic and audible vocalizations; (3) the behavioral response to aggressive attack; and (4) locomotor activity. Following a brief exposure to an attack, rats were threatened by an aggressor but protected from further attack by a wire mesh cage (30 x 21.5 x 20 cm), thereby allowing for continued behavioral and vocal measurement without the risk of physical injury; video and audio recordings were made of the attack encounter and a subset of the protected encounter (1 min). The endpoint most potently and specifically modulated by morphine was high frequency ultrasounds. The rate of high frequency calling varied as a function of the estrous cycle, supporting gonadal hormone modulation of ultrasonic vocalizations. Low frequency ultrasounds, by contrast, were relatively insensitive to opiate manipulation and were less influenced by estrous cyclicity. High frequency vocalizations may be a more sensitive indication of the affective response to an attacking conspecific that low frequency calls.(ABSTRACT TRUNCATED AT 250 WORDS)

Agonistic Behavior↗

Neurobiological mechanisms controlling aggression: preclinical developments for pharmacotherapeutic interventions.

Current pharmacotherapeutic approaches to the management of violent and aggressive behavior rely mostly on agents that act as receptor agonists or antagonists at subtypes of brain dopaminergic, GABAergic, and serotonergic receptors. Ethological experimental studies in animals have shown that drugs may modulate aggression by inhibiting motor activity, by distorting aggression-provoking or -inhibiting signals, by fragmenting behavioral sequences or temporal patterning, or by increasing the rate and intensity of aggressive acts. Evidence from animal studies points to large changes in selected brain dopamine, serotonin, and GABA systems during and following aggressive and defensive behavior. However, the specificity of drugs that are currently used to control aggressive behavior through their action as agonists or antagonists at subtypes of dopamine, serotonin or GABA receptors continues to be of concern. Similar to the effects of widely used traditional neuroleptics that nonselectively antagonize dopamine receptors, the range of behaviors which is suppressed by either D1 or D2 receptor antagonists is pervasive. At present, systemic administration of dopamine receptor antagonists in animal preparations does not target aggression-specific mechanisms. The GABAA/Benzodiazepine/Chloride ionophore receptor complex is implicated in the aggression-heightening effects of alcohol and benzodiazepines. Although early reports focused on the "taming" effects of benzodiazepine anxiolytics, low doses may enhance aggression in both animals and humans. Benzodiazepine antagonists block heightened aggression after low doses of alcohol or benzodiazepines. Agonists at certain 5-HT1 receptor subtypes such as eltoprazine are potently effective in reducing aggressive behavior of males and females of various animal species under conditions that promote charging offensive-type aggression, without adversely affecting nonaggressive components of the behavioral repertoire. However, recent reports indicate that eltoprazine and related compounds may potentiate anxiety reactions in rodents, and question the behavioral specificity of these substances. Opioid receptor antagonists modulate primarily physiological and behavioral responses of defense and submission. Defeated animals show tolerance to opiate analgesia and withdrawal responses upon challenge with opioid receptor antagonists. Defensive and submissive vocalizations are potently blocked by opioid peptides. Substances that target specific receptor subtypes at serotonergic, GABAergic and opioidergic synapses are most promising for the selective modification of aggressive, defensive and submissive behavior patterns.

Aggression↗

Effect of carboxyhemoglobin on the accuracy of mixed venous oximetry monitors in dogs.

OBJECTIVE: To assess the accuracy of mixed venous hemoglobin oxygen saturation estimated, using in vivo pulmonary artery reflectance oximetry with ranging concentrations of carboxyhemoglobin. DESIGN: Criterion standard, a comparison of an alternative test to the "gold standard." SETTING: Laboratory animal facility of a large university. SUBJECTS: Five mongrel dogs. INTERVENTIONS: Anesthetized dogs were mechanically ventilated to normocarbia and instrumented with arterial catheters and pulmonary artery oximetry catheters. The dogs were ventilated with increasing inspired concentrations of carbon monoxide, and blood samples were analyzed for fractional concentrations of oxyhemoglobin and carboxyhemoglobin. Carboxyhemoglobin levels ranged from 0% to 70%. At each level of carboxyhemoglobin, FIO2 was varied from 0.21 to 0.09. Co-oximeter readings were compared with mixed venous oxygen saturation measurements of the pulmonary artery oximetry catheter. MEASUREMENTS AND MAIN RESULTS: Mixed venous oxygen saturation measurements from the pulmonary artery oximetry catheter system progressively overestimated fractional oxyhemoglobin in the presence of carboxyhemoglobin. This catheter's mixed venous oxygen saturation reading could be corrected for the presence of carboxyhemoglobin by a derived formula. Regression analysis for corrected mixed venous oxygen saturation (calculated) vs. fractional oxyhemoglobin yields a slope and intercept of 0.98 and -1.01, respectively, with a correlation coefficient of .98. The bias and precision values for fractional oxyhemoglobin vs. mixed venous oxygen saturation (calculated) are 1.9 and 2.2 (n = 66), with bias representing the degree of systematic error or deviation from the true measurement, and precision representing the confidence limits (or standard deviation) for individual variations from the true measurement. CONCLUSIONS: Mixed venous oxygen saturation monitoring does not detect the presence of carboxyhemoglobin and progressively overestimates fractional oxyhemoglobin as carboxyhemoglobin increases. Mixed venous oxygen saturation values of the standard pulmonary artery oximetry catheter approximately equal functional hemoglobin saturation. Bench co-oximeter blood analysis is required in patients suspected of having increased carboxyhemoglobin levels.

Algorithms↗

Ultrasounds during agonistic interactions between female rats (Rattus norvegicus).

Defensive and vocal behaviors of 18 female Long-Evans rats (Rattus norvegicus) in encounters with aggressive, lactating conspecifics were examined in order to determine if female rats emit ultrasounds during agonistic interactions and to characterize any such calls. The subjects, selected during estrus or diestrus, were exposed to 1-min attacks at 25-min intervals. Between attacks the subjects were threatened by the aggressor but protected by a wire-mesh cage. Female rats emitted both high- (32-60 kHz) and low-frequency (20-32 kHz) ultrasonic calls in agonistic encounters, with the rate of high-frequency calls enhanced during estrus. Low-frequency ultrasounds were shorter in duration and higher in frequency than those emitted by male rats in similar conditions. We conclude that female rats emit ultrasonic calls during defensive responding and that the characteristics and rate of calling vary as functions of sex and gonadal hormone state.

Agonistic Behavior↗

An easy approach to laparoscopic cholangiography.

Laparoscopic cholecystectomy has become the procedure of choice for surgical removal of the gallbladder. Intraoperative cholangiography is often needed to define ductal anatomy and to detect choledocholithiasis, a procedure which often proves more difficult than its open counterpart. Several newer cholangiocatheters have been introduced which have made laparoscopic cholangiography easier, however, the standard approach through an existing operating port will usually place the catheter at an odd angle, making catheterization of the cystic duct all but impossible in some cases. To avoid this acute angle between the catheter and the cystic duct, the authors have begun using a standard central line introducer as the port through which the catheter is inserted. When placed in the proper position through the lateral abdominal wall, this approach allows the catheter to be inserted parallel and in line with the cystic duct for much easier and faster cannulation.

Catheterization↗

Effect of early exposure to delta-9-tetrahydrocannabinol on the levels of opioid peptides, gonadotropin-releasing hormone and substance P in the adult male rat brain.

The effects of neonatal exposure to delta-9-tetrahydrocannabinol (THC) on the adult animal brain neurochemistry and pain perception were evaluated. Newborn rat pups were culled to a litter size of 8 (males and females) and treated either with THC (2 mg/kg) or oil (control) daily, during days 1-4 after birth. After weaning, the THC-treated males were housed 4 per cage. During the juvenile period (day 50), the THC-treated animals exhibited significantly lower baseline tail-flick values (a measure of pain perception) than the control. However, as adults, the THC-treated animals exhibited significantly higher sensitivity to pain following 5 mg/kg morphine challenge. Furthermore, the THC-treated animals had significantly elevated beta-endorphin and methionine-enkephalin levels in almost all the brain areas sampled for the study. In addition, the neonatally THC-treated rats exhibited significantly higher levels of substance P (SP) and significantly lower levels of gonadotropin releasing hormone (GnRH) in the anterior hypothalamus-preoptic area. The SP and GnRH levels did not differ among the THC-treated and control animals in the medial basal hypothalamus. The results of this study indicate that even a very low dose of THC administered during the neonatal period has a long-lasting effect on the brain neurochemistry. In particular, neonatal administration of THC appears to alter functioning of the endogenous opioid system.

Animals↗

Morphine effects on maternal aggression, pup care and analgesia in mice.

In order to assess the respective contribution of opioid receptors to the behavioral and physiological characteristics of lactating animals, we challenged mice with morphine at different phases of the lactation period. Sensitivity to morphine's effects on aggressive behavior, pup care, pain response and body temperature were measured. Lactating mice were assigned to 1 of the 3 weeks of lactation and to 1 of 5 doses of morphine sulfate (0, 1, 3, 6, 10 mg/kg IP). After morphine administration, rectal temperature and tail flick were assessed. Behavior towards three pups was observed for 5 min, followed by an aggression test with a female intruder. Morphine significantly increased the latency to retrieve pups and decreased aggressive behavior at doses that do not decrease motoric activity. Compared to virgin mice, lactating females are less sensitive to the analgesic actions of morphine but similarly sensitive to its hypothermic properties. The fact that virgin and lactating females can be distinguished on the basis of their sensitivity to morphine-induced analgesia suggests that lactating animals undergo functionally relevant changes in opioid regulation of pain sensitivity. Furthermore, morphine's specific and potent inhibition of pup retrieval supports the hypothesis that decreased opioid peptide activity is important for the expression of certain postpartum behaviors.

Aggression↗