"Coffee, tea and me": moderate doses of caffeine affect sexual behavior in female rats

The present study evaluated the effects of acute caffeine administration on paced mating behavior and partner preference in ovariectomized rats primed with estrogen and progesterone. In Experiment 1, female rats were tested for paced mating behavior following acute administration of caffeine (15 mg/kg). Caffeine shortened the latency to return to a male following an ejaculation. Although this dose of caffeine did not alter the likelihood of leaving a male after receiving sexual stimulation, locomotor activity did increase significantly. Experiment 2 evaluated the dose response characteristics of caffeine (7.5, 15, 30 mg/kg) administration on paced mating behavior. Replicating Experiment 1, caffeine at the lower doses shortened the latency to return to a male following an ejaculation. Finally, to determine whether the effects of caffeine (15 mg/kg) on contact-return latency reflect a change in sexual motivation or merely an inability to inhibit locomotion, rats were tested for partner preference (intact male vs. estrous female) following caffeine administration (Experiment 3). Although caffeine did not disrupt preference for a sexual partner, caffeine selectively increased visits to the male when physical contact was possible. Collectively, these results suggest that the effects of caffeine on female mating behavior may reflect an increase in both sexual motivation and locomotor activity.     

Effects of yohimbine and idazoxan on motor behaviors in male rats.

Yohimbine, an alpha 2 adrenergic antagonist, facilitates copulatory behaviors in male rats. This facilitation may reflect nonspecific activation of behavior rather than a more selective activation of copulatory behaviors. The present experiments assessed the effects of yohimbine on locomotor behaviors at a dose (2.0 mg/kg) known to facilitate sexual behaviors. Experiment 1 used a computer pattern-recognition system to classify motor behaviors into specific acts and act groups. Male albino rats were tested in three conspecific conditions: estrous female, anestrous female, or no conspecific. Yohimbine decreased locomotor activity in all three conspecific conditions. Experiment 2 examined the effects of yohimbine (2.0 mg/kg) and amphetamine (1.0 mg/kg) on locomotor behavior in a photocell-equipped activity measurement system. Amphetamine increased and yohimbine decreased locomotor activity. Experiment 3 used the computer pattern-recognition system to compare the effects of yohimbine and idazoxan, another alpha 2 adrenergic antagonist, on motor behaviors. Yohimbine and idazoxan both decreased activity but produced different patterns of behavioral change. The facilitatory effects of yohimbine on copulatory behaviors at a dose of 2.0 mg/kg are apparently not mediated by nonspecific activation of behavior.     

Sexual-incentive motivation and paced sexual behavior in female rats after treatment with drugs modifying dopaminergic neurotransmission

The effects of the dopamine receptor agonist apomorphine, the dopamine releaser amphetamine, and the dopamine receptor antagonist cis(Z)-flupenthixol on sexual-incentive motivation and on paced-mating behavior were studied in female rats. Apomorphine, in the doses of 0.125 and 0.5 mg/kg, showed a tendency to reduce incentive motivation. Ambulatory activity was inhibited, evidenced both by diminished distance moved and reduced velocity of movement. Amphetamine (0.25 and 1 mg/kg) and flupenthixol (0.25 and 0.5 mg/kg) failed to modify incentive motivation while stimulating and reducing ambulatory activity, respectively. In the mating test, apomorphine enhanced the latency to enter the male's half and reduced the number of proceptive behaviors. However, these effects were associated with the appearance of stereotyped sniffing. Amphetamine increased the propensity to escape from the male after a mount without having other effects. Flupenthixol augmented the duration of the lordosis posture. Neither amphetamine nor flupenthixol affected sniffing. These data show that facilitated dopaminergic neurotransmission stimulates neither paced female sexual behavior nor sexual-incentive motivation. Dopamine receptor blockade has slight consequences. It is concluded that dopamine is not a transmitter of major importance for unconditioned female sexual motivation and behavior.     

Intracranial infusions of amphetamine into the medial preoptic area but not the nucleus accumbens affect paced mating behavior in female rats

The present study evaluated the effects of intracranial administration of amphetamine (AMPH) on paced mating behavior and open field activity in sexually receptive female rats. In Experiment 1, AMPH (0.5 microl of 10 microg/microl) or vehicle was infused bilaterally into the medial preoptic area (mPOA). In Experiments 2 and 3, AMPH (0.5 microl of 40 microg/microl) or vehicle was infused bilaterally into the shell region of the nucleus accumbens (NAc) or core region of the NAc, respectively. In Experiment 1, infusions of AMPH into the mPOA increased the latency to return to the male following sexual stimulation without affecting locomotor activity in the open field test. However, when AMPH was infused 3.0 mm dorsal to the mPOA, no effects were observed. In Experiments 2 and 3, infusions of AMPH into the NAc shell or core significantly increased locomotor activity during the open field test but failed to affect most measures of paced mating behavior. Together these results suggest that amphetamine-stimulate dopamine release in the mPOA but not in the NAc alters paced mating behavior, confirming previous conclusions that the mPOA plays a critical role in female sexual behavior, whereas the NAc plays a relatively limited role.     

Differential behavioral responses to chronic amphetamine in adult male and female rats exposed to postnatal cocaine treatment.

The impact of cocaine exposure during development on behavioral sensitization as measured by locomotor activity and stereotypy following repeated intermittent administration of amphetamine is examined. Male and female Sprague-Dawley rats were exposed to cocaine at 50 mg/kg/day during postnatal days (PND) 11-20 and, as adults (PND193-212), were administered seven daily injections of 2.0 mg/kg amphetamine. Both locomotor activity and stereotypic behavior were assessed following the first and seventh injections. Control males and females showed sensitized behavior following repeated amphetamine injections with females showing greater locomotion while males showed increased stereotypy. Male rats pretreated with cocaine failed to develop sensitized locomotor or stereotypic responses following repeated amphetamine injections consistent with dampened D(1) receptor activity. Females pretreated with cocaine did not show a sensitized locomotor response but did display sensitization of stereotypy following repeated amphetamine administration. Thus, it appears that postnatal cocaine treatment produces differential effects on the circuits mediating sensitization behavior in male and female rats.     

Effects of D-amphetamine on defensive behaviors related to fear and anxiety

In rodents, the administration of amphetamine has been associated with increased locomotor activity and stereotypy, and an emerging body of evidence suggests that it also enhances anxiety-like behavior in a number of animal models. Ethoexperimental analyses have outlined an array of defensive behaviors to threat that are responsive to anxiolytic, panicolytic-like and panicogenic agents, suggesting that the characterization of amphetamine effects on defense may provide further insights into the emotionality consequences of this drug. In Experiment 1, intraperitoneal administration of amphetamine (1 and 5 mg/kg, i.p.) on defensive behavior elicited by a predatory threat stimulus was assessed via time sampling analysis. Amphetamine dose-dependently suppressed freezing while potentiating locomotor activity. In Experiment 2, amphetamine was administered intravenously and animals were tested in a Rat Runway Test (RRT), designed to individually elicit a variety of defensive behaviors to a conspecific threat. All three doses of amphetamine (1, 2 and 5 mg/kg) produced robust changes in defensive responding by increasing directional flight behavior, jump escapes and upright/orientations. The results are in agreement with those of another psychostimulant, cocaine, and support a previously hypothesized link between flight and panic.     

Effects of naloxone and diprenorphine on amphetamine-stimulated behavior in guinea pigs and rats

Amphetamine (0.1-10 mg/kg), naloxone (0.1-10 mg/kg) and diprenorphine (0.03-10 mg/kg) were studied for their ability to modulate locomotor behavior in the guinea pig. Naloxone, administered alone, caused a non-significant decrease in locomotor activity and had a similar non-significant effect on amphetamine-stimulated activity. Diprenorphine induced a significant suppression of locomotor activity, the magnitude of which was inversely related to dose: smaller doses of diprenorphine caused a greater suppression of locomotor activity than larger doses. Two doses of diprenorphine (0.1 and 1.0 mg/kg) were tested in combination with amphetamine in the guinea pig. They significantly reduced amphetamine-stimulated behavior and were equipotent in this regard. In contrast, diprenorphine had no effect on amphetamine-stimulated activity in rats. However, in keeping with other reports, naloxone (10 mg/kg) significantly reduced amphetamine-stimulated behavior. The differences in the actions of diprenorphine and naloxone on the behavior of guinea pigs and rats may reflect a different underlying distribution of subtypes of opioid receptor in the two species.     

Delta opioid receptor ligands modulate anxiety-like behaviors in the rat

The role of the delta opioid receptor in regulating anxiety-like behavior in male Sprague-Dawley rats was examined.Using an elevated plus maze, the effects of the selective delta opioid receptor antagonist naltrindole (1 or 5 mg kg(-1)) and agonist SNC80 (1, 5 or 20 mg kg(-1)) on anxiety-like behavior were measured. Anxiety was also measured following administration of diazepam (3 mg kg(-1)) and amphetamine (1 mg kg(-1)) and compared to the effects of SNC80. Locomotor activity following administration of naltrindole, SNC80, diazepam, and amphetamine was measured. Finally, the defensive burying paradigm was used to confirm the findings from the elevated plus maze.Results demonstrated that SNC80 produced dose-dependent anxiolytic effects similar to that of the classical antianxiety agent, diazepam. Administration of naltrindole caused anxiogenic behavior in rats further supporting the involvement of the delta opioid receptor system in regulating anxiety. Naltrindole also blocked the anxiolytic effects of SNC80. Amphetamine had no effect on anxiety-like behavior. SNC80 induced hyperactivity similar to amphetamine at the doses tested, while naltrindole and diazepam did not significantly affect locomotor activity.Although SNC80 can increase locomotor activity, control experiments reported herein indicate that hyperlocomotion is not sufficient to produce an anxiolytic response on the elevated plus maze. Together with the results from the defensive burying paradigm, this suggests that the effects of SNC80 on reducing anxiety are independent of its effects on locomotion. Collectively these data show that the delta opioid receptor system can regulate anxiety-like behavior in an anxiolytic (agonist) and anxiogenic (antagonist) manner.     

Sensitized activation of Fos and brain-derived neurotrophic factor in the medial prefrontal cortex and ventral tegmental area accompanies behavioral sensitization to amphetamine

Behavioral sensitization, or augmented locomotor response to successive drug exposures, results from neuroadaptive changes contributing to addiction. Both the medial prefrontal cortex (mPFC) and ventral tegmental area (VTA) influence behavioral sensitization and display increased immediate-early gene and BDNF expression after psychostimulant administration. Here we investigate whether mPFC neurons innervating the VTA exhibit altered Fos or BDNF expression during long-term sensitization to amphetamine. Male Sprague-Dawley rats underwent unilateral intra-VTA infusion of the retrograde tracer Fluorogold (FG), followed by 5 daily injections of either amphetamine (2.5 mg/kg, i.p.) or saline vehicle. Four weeks later, rats were challenged with amphetamine (1.0 mg/kg, i.p.) or saline (1.0 mL/kg, i.p.). Repeated amphetamine treatment produced locomotor sensitization upon drug challenge. Two hours later, rats were euthanized, and mPFC sections were double-immunolabeled for either Fos-FG or Fos-BDNF. Tissue from the VTA was also double-immunolabeled for Fos-BDNF. Amphetamine challenge increased Fos and BDNF expression in the mPFC regardless of prior drug experience, and further augmented mPFC BDNF expression in sensitized rats. Similarly, more Fos-FG and Fos-BDNF double-labeling was observed in the mPFC of sensitized rats compared to drug-naïve rats after amphetamine challenge. Repeated amphetamine treatment also increased VTA BDNF, while both acute and repeated amphetamine treatment increased Fos and Fos-BDNF co-labeling, an effect enhanced in sensitized rats. These findings point to a role of cortico-tegmental BDNF in long-term amphetamine sensitization.     

Early social isolation, but not maternal separation, affects behavioral sensitization to amphetamine in male and female adult rats.

Early life stressful manipulations, such as maternal separation (MS) or social isolation (SI), can influence the neurobiological development of rats and alter the response of adult animals to drugs of abuse. The present study examined the acute and sensitized behavioral responses (locomotor activity (LMA) and stereotypy) induced by amphetamine after MS or SI in male and female rats. In addition, the hypothesis that the combination of SI and MS could lead to additional effects on the behavioral response to amphetamine was tested. After the repetitive, intermittent administration of 1.5 mg/kg D-amphetamine over five consecutive days, the behavioral expression of sensitization to a challenge injection was assessed following a 2-day withdrawal period. In both sexes, MS and SI did not alter the acute locomotor activating effects of amphetamine as measured in the open-field environment after the first administration of the drug. Whereas SI altered the expression of sensitization to amphetamine in both sexes, MS did not affect it. Finally, in none of the behavioral variables measured did MS and SI interact to further modify the behavioral profile of the animals. The present results suggest that a postweaning manipulation of the environment (SI) is more effective than a preweaning manipulation (MS) in modifying the expression of sensitization to amphetamine.     

Naloxone inhibits mating and conditioned place preference for an estrous female in male rats soon after castration

Three experiments were conducted to assess the role of endogenous opioids in controlling mating behavior and sexual reward in the male rat. In Experiment 1 SC administration of naloxone (0.5, 1.0, 5.0, or 10.0 mg/kg) significantly reduced mounting and ejaculation in male rats tested 14, but not 7 days, after castration. In Experiment 2 naloxone (5.0 mg/kg) administered SC to gonadally intact males, which had ejaculated repeatedly with one female until they were sexually sated, significantly inhibited the resumption of mating after the reintroduction of a female partner. One interpretation of these results is that naloxone attenuated the reward experienced by castrated and sexually sated males in the presence of an estrous female, thereby disrupting males' coital performance. This hypothesis was tested in Experiment 3 using a conditioned place preference paradigm in which males copulated with an estrous female in an initially "non-preferred" (white) compartment, whereas on alternate days they remained alone in an initially "preferred" (black) compartment. After 10 such conditioning sessions, males were either castrated or sham-operated. They later were given free access to both compartments in the absence of an estrous female. Seven days after conditioning and surgery, sham-operated, naloxone-injected males and both groups of castrates spent significantly less time than sham-operated, saline-injected controls in the initially "non-preferred" compartment. Fourteen days after conditioning and surgery castrated, naloxone-treated males spent significantly less time in the "non-preferred" compartment than males in the other three groups. Endogenous opioids may play an important role in the interpretation by males of the incentive motivational stimuli which emanate from an estrous female.     

Methamphetamine enhances sexual behavior in female rats

The present study evaluated the effects of methamphetamine (MA) on sexual behavior in female rats. In Experiment 1, ovariectomized, hormone-primed rats were injected with MA (1.0 mg/kg, i.p.) or saline prior to a test for mate choice wherein females could mate with two males simultaneously. Female rats treated with saline returned to their preferred mate faster after receiving intromissions and visited their preferred mate at a higher rate than their non-preferred mate. In contrast, MA-treated female rats spent a similar amount of time with their preferred and non-preferred mate and failed to return to their preferred mate faster than to their non-preferred mate following intromissions. Two weeks later, the females received the same drug treatment but were tested for partner preference wherein females could spend time near a male or female stimulus rat. All subjects spent more time near the male stimulus than the female stimulus. However, the MA-treated rats visited the male stimulus more frequently and spent less time near the female stimulus than the saline-treated rats. Similar to Experiment 1, female rats in Experiment 2 were tested for mate choice and then two weeks later tested for partner preference; however, females received three daily injections of MA (1.0 mg/kg, i.p.) or saline. Females treated chronically with MA returned to both males faster following intromissions than females treated with saline, independent of preference (i.e., preferred mate and non-preferred mate). Furthermore, MA-treated rats were more likely to leave either male (i.e., preferred or non-preferred mate) than saline-treated rats after receiving sexual stimulation. Although MA-treated subjects spent more time near the male stimulus than the female stimulus, they spent less time near either when compared to saline-treated subjects. The present results demonstrate that MA affects sexual behavior in female rats partly by increasing locomotion and partly by directly affecting sexual behavior.     

Effects of morphine, beta-endorphin and naloxone on catecholamine levels and sexual behavior in the male rat

Intraperitoneal administration of the opiate antagonist naloxone hydrochloride (30 mg/kg) to sexually experienced male rats caused a significant reduction in mount and intromission latencies, number of mounts preceding ejaculation and ejaculation latencies. Intraperitoneal adminstration of naloxone (30 mg/kg) also stimulated persistant non-copulators to begin mating and to ejaculate within a twenty minute test period. Conversely, intraperitoneal administration of morphine sulphate (6 mg/kg) as well as intraventricular injection of the endogenous opiate beta-endorphin (6 micrograms) produced a complete loss of copulatory behavior in male rats. The deficit in sexual behavior induced by beta-endorphin was correlated with a significant increase in hypothalamic norepinephrine levels. It is suggested that the endogenous opiates may be involved in the mediation of sexual behavior via an interaction with central catecholaminergic systems.     

Female and male rats in late adolescence differ from adults in amphetamine-induced locomotor activity, but not in conditioned place preference for amphetamine

Rodent models display differences in drug-induced behaviour between prepubertal/young adolescents and adults that parallel developmental differences in people; however, little is known as to when the transition to 'adultlike' behaviour occurs. We investigated the differences in locomotor and reward responses to amphetamines in male and female rats in late adolescence and compared them with corresponding adult responses. Long-Evans rats were tested for locomotor activity and conditioned place preference (CPP) for amphetamine (0.25, 0.5 or 1.0 mg/kg), beginning at 45 or 69 days of age. Adolescent female rats moved less to the first injection of amphetamine compared with adult female rats irrespective of dose, whereas adolescent male rats did not differ from adults. Adolescent female rats significantly increased locomotor activity in response to subsequent injections of amphetamine at all three doses, whereas such sensitization was only found at the highest dose for adult female and male rats. No effect of repeated injections at any dose was observed in adolescent male rats. No age differences were observed in CPP, but female rats showed greater CPP during the dioestrous than during the oestrous phase of the cycle. These data suggest that differences in neural systems underlying some behavioural responses to amphetamine continue to mature postpubertally into late adolescence in a sex-specific manner.     

Effects of serotonergic manipulations on the behavioral sensitization and disinhibition associated with repeated amphetamine treatment

This study investigated the effects of repeated amphetamine treatment on locomotor activity and behavioral inhibition in the elevated plus-maze, and the influence of serotonin (5-HT) neurotransmission on these behaviors. Acute administration of amphetamine (1.0 mg/kg subcutaneously [SC]) stimulated locomotor activity, which was attenuated by acute citalopram (5.0 mg/kg SC) pretreatment. Repeated daily treatment with amphetamine (15 days) sensitized the rats to the amphetamine-induced locomotor stimulation. Acute pretreatment with the 5-HT precursor l-5-hydroxytryptophan (5-HTP; 25 mg/kg IP) or chronic treatment with the selective 5-HT reuptake inhibitor citalopram (5.0 mg/kg SC, twice daily), did not alter the expression of amphetamine-induced locomotor sensitization. In the elevated plus-maze, animals subjected to repeated amphetamine treatment expressed behavioral disinhibition after amphetamine exposure (1.0 mg/kg SC; -35 min), which was antagonized both by acute 5-HTP and chronic citalopram treatment. In summary, these findings suggest that behavioral sensitization to amphetamine is associated with amphetamine-induced behavioral disinhibition, and that acute 5-HTP as well as chronic citalopram treatment counteract the expression of amphetamine-induced behavioral disinhibition, but not locomotor sensitization. It appears likely that the antagonistic effects of 5-HTP and citalopram on behavioral disinhibition derive from a drug-induced facilitation of brain 5-HT neurotransmission.     

Susceptibility to amphetamine-induced locomotor sensitization is modulated by environmental stimuli.

We have previously reported that intravenous (i.v.) administrations of 0.5-1.0 mg/kg of amphetamine in the absence of any environmental stimuli predictive of drug administration failed to induce psychomotor sensitization whereas the same drug did produce robust sensitization when given in association with environmental novelty. These results were obtained by studying rotational behavior in animals with a unilateral 6-OHDA lesion of the mesostriatal dopamine system. The purpose of this study was to determine if environmental novelty has a similar effect on sensitization to the locomotor activating effects of amphetamine in neurologically intact rats. Rats were implanted with i.v. catheters and divided in four groups. Two groups were housed in locomotor activity cages and given seven consecutive i.v. infusions of either saline (SAL-HOME group) or 0.375 mg/kg of amphetamine (AMPH-HOME group), using a remotely activated delivery system. Simultaneously, the other two groups were transported to the test cages and given the same treatment (SAL-NOVEL and AMPH-NOVEL groups). After one week withdrawal, all groups were given an amphetamine challenge (0.375 mg/kg, i.v.). Amphetamine sensitization developed when the drug was administered under NOVEL conditions, as indicated by a progressive increase in amphetamine-induced locomotor activity over test sessions and by a greater response to the amphetamine challenge in the AMPH-pretreated versus the SAL-pretreated group. In contrast, no sensitization was observed under HOME conditions. Similar results were obtained with the analysis of vertical activity.     

Satellite symposium of the 7th international congress of pharmacology

The locomotor stimulant and stereotypic effects of amphetamine were investigated in rats pretreatment with the specific dopaminergic blocker spiperone (0.25 mg/kg). Amphetamine doses from 8.0 to 64.0 mg/kg failed to stimulate behavior significantly and consistently after spiperone treatment. These results suggest the possibility of non-competitive antagonism by spiperone at dopaminergic synapses.     

Contribution of drug doses and conditioning periods to psychomotor stimulant sensitization

Rationale Repeated intermittent administration of psychostimulant drugs such as amphetamine and cocaine can cause sensitization (reverse tolerance) to the locomotor-stimulating actions in rats. Sensitization to the stimulant effects of these drugs might contribute to the development and maintenance of addictive behaviors (e.g. compulsive drug use).Objectives Studies were designed to systematically examine how testing conditions affect the development and expression of locomotor sensitization to cocaine and amphetamine.Methods Rats were treated once daily with intraperitoneal (i.p.) administration of amphetamine (0.5–2.0 mg/kg) or cocaine (5.0–20 mg/kg) and placed in activity chambers for 30, 60, or 120 min. All amphetamine-preexposed rats were challenged with 0.5 mg/kg amphetamine, and all cocaine-preexposed rats were challenged with 5.0 mg/kg cocaine for 120-minute activity tests 2 weeks after the final injection.Results Rats treated repeatedly with 2.0 mg/kg amphetamine and tested for 60 min in activity chambers or 20 mg/kg cocaine and tested for 30 min in activity chambers were most active in response to the drug challenge. These time points coincide with the maximal behavioral effects of each drug, as measured after the first injection. In contrast, rats treated with 2.0 mg/kg amphetamine and tested for 30 min or 20 mg/kg cocaine and tested for 120 min were least active in response to the drug challenge.Conclusions Repeated association of the peak behavioral effects of high doses of amphetamine or cocaine with the drug-paired environment produces maximal expression of sensitized locomotor responses. Certain testing conditions appear to disrupt sensitization to these same doses of the drugs.     

Locomotor activity and stereotypy in rats following repeated apomorphine treatments at 1-, 3-, or 7-day intervals

In two experiments, the effects of repeated intermittent administration of a relatively high dose of apomorphine (5 mg/kg) on locomotor activity and/or stereotypic behavior in rats was determined. In Experiment 1, male rats were given ten subcutaneous (SC) injections of apomorphine or vehicle and tested for locomotor activity and stereotypy. The first nine injection test sessions were given at 3-day intervals and the tenth injection test session was given 18 days following the ninth session. In Experiment 2, male rats were tested for locomotor activity following ten SC injections of apomorphine or vehicle with either a one- or seven-day interval between injections. Major findings were as follows: a) apomorphine produced progressively greater increases in locomotor activity with each succeeding injection (i.e., sensitization); b) sensitization to the locomotor activity stimulating effects of apomorphine developed with interinjection intervals of one, three, and seven days; c) the sensitization effect was maintained over the 18-day drug-free break; and d) the effect of apomorphine on stereotypic behavior did not significantly change with repeated injections. These findings indicate that even a single dose of apomorphine induces relatively long-lasting neurobiological changes. Moreover, these findings are consistent with the view that separate neural pathways mediate locomotor activity and stereotypy in rats.     

Naltrexone blocks amphetamine-induced hyperactivity,but not disruption of social and agonistic behavior in mice and squirrel monkeys

Significant anatomical overlap of opioid and dopamine receptors as well as reciprocity of control over synthesis, metabolism, and release of opioid peptides and dopamine in brain suggests functional interactions between the two systems. In the first of two studies, the behavioral effects of amphetamine and naltrexone alone, and in combination were studied in established groups of socially interacting squirrel monkeys. Naltrexone (0.1–10.0 mg/kg, IM) increased locomotion and marking behavior in subordinate monkeys. The frequency of social initiatives directed at treated subordinate monkeys by untreated members of the group was also increased. The behavior of dominant monkeys was relatively unaffected, except at the highest dose when autonomic distress was also evident. The frequency of walking bouts by both dominant and subordinate monkeys was increased by amphetamine (0.1–0.6 mg/kg, IM), and the social behavior of dominant monkeys was disrupted by drug treatment. Naltrexone (0.1 mg/kg, IM) significantly antagonized amphetamine's effects on motor behavior, and enhanced or did not affect amphetamine's effects on social behavior. In a second study, the interaction of amphetamine (0.63–10.0 mg/kg, IP) and naltrexone (0.1–10.0 mg/kg, IP) on the behavior of resident male mice during confrontations with a male intruder was studied. Naltrexone selectively reduced the frequency of attack at the highest dose tested. Amphetamine increased locomotor activity and decreased attack and threat behavior in resident mice. A low dose of naltrexone (1.0 mg/kg, IP) blocked amphetamine's effects on locomotion and enhanced the disruption of aggressive behavior. The amphetamine-naltrexone interaction on locomotor activity in mice and monkeys is consistent with opioid receptor modulation of dopamine mediated functions. However, this mechanism does not appear to account for the interaction of naltrexone and amphetamine on social behavior.