Medications for stimulant abuse: Agonist-based strategies and preclinical evaluation of the mixed-action D? partial agonist aripiprazole (Abilify?).

The utility of full and partial agonists for the management of opioid addiction and smoking behavior has encouraged the development of dopamine partial agonist-based medications for treating monoaminergic stimulant abuse and addiction. Aripiprazole, a recently introduced atypical antipsychotic with D? partial agonist actions, has been studied in mice, rats, and man, but its ability to attenuate abuse- and addiction-related effects of cocaine or methamphetamine remains controversial. The present studies in monkeys were conducted to further evaluate aripiprazole as a candidate medication. The effects of aripiprazole on overt behavior were first compared with those of other dopamine-related drugs. In contrast to D? full agonists, aripiprazole did not induce self-scratching. Like D? receptor blockers, however, aripiprazole occasioned dose-related increases in catalepsy-associated behavior that, at the highest doses, were characterized most prominently by periods of stillness and immobility. In methamphetamine-discrimination experiments, aripiprazole did not engender responding on the methamphetamine-associated lever; rather, aripiprazole antagonized the discriminative-stimulus effects of methamphetamine by shifting its dose-effect function rightward. In self-administration "choice" experiments, acute or chronic treatment with aripiprazole did not attenuate the reinforcing strength of intravenous cocaine relative to food delivery. However, like D? full agonists, priming injections of aripiprazole prior to sessions of intravenous saline availability engendered comparable levels of responding on levers leading to food delivery and intravenous injections. The present findings indicate that agonist and antagonist effects of aripiprazole are evident under different experimental conditions and that, like D? full agonists, aripiprazole may have limited value for treating monoaminergic stimulant abuse and addiction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A history of postponing shock does not appear to alter the discriminative stimulus effects of cocaine

Previous research has shown that the rate of punished lever pressing of monkeys is typically decreased by cocaine administration. However, cocaine increases punished responding in monkeys with a history of responding maintained by the postponement of shock presentation. This raises the question of whether other behavioral effects of cocaine differ following a history of postponing shock. The present experiment examined whether a history of postponing shock alters the discriminative stimulus effects of cocaine. Three squirrel monkeys were trained to discriminate cocaine (0.56 mg/kg, intramuscular) from saline. Presses on the left lever produced food following saline injections whereas presses on the right lever were reinforced following administration of cocaine. Occasional test sessions were conducted in which cocaine (0.1-0.56 mg/kg), midazolam (0.03-0.56 mg/kg) or pentobarbital (0.3-5.6 mg/kg) was injected prior to the session and responding on either lever was reinforced. Discrimination training was discontinued during a second experimental phase in which responding was maintained by shock postponement. Pulling a chain postponed mild shocks for 25 s, whereas shocks occurred every 5 s in the absence of responding. Next, the drug discrimination dose-response curves were redetermined. The dose-response curves for all drugs before and after the shock postponement history were similar. This outcome suggests that the influence of a history of shock postponement is specific to punished responding.     

Effects of d-amphetamine and cocaine on strained ratio behavior in a repeated-acquisition task

Pigeons acquired a different four-response chain each session by responding sequentially on three keys in the presence of four colors. When the fixed-ratio requirement for food presentation was five completions of the chain, d-amphetamine and cocaine disrupted the behavior. As the dose of each drug was increased, the overall response rate decreased, the overall accuracy was impaired (i,e., percent errors increased), and there was less within-session error reduction (acquisition). In contrast, when the fixed-ratio requirement was either 20 or 50 completions of the chain, certain doses of both drugs produced large increases in the overall response rate by eliminating the extended pausing (ratio strain) that was characteristic of the control sessions. These rate-increasing effects were accompanied by error-decreasing effects, both during acquisition and after the response chain had been acquired. Taken together, the results show that the effects of d-amphetamine and cocaine on behavior in a repeated-acquisition task can be modulated by manipulating the value of the fixed-ratio schedule maintaining the behavior.     

Evidence that an OX-2-positive cell can inhibit the stimulation of type 1 cytokine production by bone marrow-derived B7-1 (and B7-2)-positive dendritic cells

The present study was designed to compare the effects of typical and atypical antipsychotic drugs on extracellular dopamine (DA) levels in the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAC), using in vivo microdialysis with dual probe implantation in awake, freely moving rats. Amperozide (2 and 10 mg/kg), clozapine (5 and 20 mg/kg), and olanzapine (10 mg/kg), all of which are atypical antipsychotics, produced greater increases in extracellular DA levels in the mPFC than in the NAC. Olanzapine (1 mg/kg), risperidone (0.1 and 1 mg/kg), also an atypical antipsychotic, and S-(-)-sulpiride (25 mg/kg), a typical antipsychotic, produced comparable increases in extracellular DA levels in the mPFC and the NAC. S-(-)-sulpiride (10 mg/kg) and haloperidol (0.1 and 1 mg/kg), another typical antipsychotic, significantly increased extracellular DA levels in the NAC but not in the mPFC. The effects of the six antipsychotic drugs to increase extracellular DA levels in the mPFC relative to those in the NAC was positively correlated with the difference between their pKi values for serotonin (5-hydroxytryptamine, 5-HT2A) and DA-D2 receptors and was inversely correlated to their pKi values for D2 or D3 receptors, but was not for 5-HT2A receptors alone. These results are consistent with the hypothesis that the ability of antipsychotic drugs to produce a greater increase in prefrontal compared with NAC extracellular DA levels may be related, in part, to weak D2 and D3 receptor affinity relative to 5-HT2A receptor antagonism.     

Acquisition of intravenous cocaine self-administration with concurrent access to food in cynomolgus monkeys.

The present study used a concurrent schedule of food and drug delivery in socially housed male cynomolgus monkeys (Macaca fascicularis; N?=?15) to study variables that influence cocaine acquisition. Each monkey was implanted with subcutaneous vascular access ports, and responding was maintained under a concurrent food, saline schedule with the lever associated with each stimulus presentation varied daily. Next, increasing cocaine doses (0.003–0.3 mg/kg/inj) were concurrently available with food for at least 5 consecutive sessions per dose. Under these conditions, an unexpected lever bias emerged in all 15 monkeys. The development of the lever bias could not be predicted on the basis of cocaine dose or total intake and was not related to social rank. These findings suggest that in monkeys, concurrent fixed-ratio schedules of food and cocaine presentation may result in persistent biased responding that overshadows cocaine preference in studies of acquisition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Determination of the place conditioning and locomotor effects of amperozide in rats: A comparison with cocaine.

Amperozide promotes social interactions in rats (Rattus norvegicus) and reduces craving for cocaine and alcohol without producing adverse side effects. Amperozide administration produced a place preference in the dose range from 3.0 to 10.0 mg/kg. Locomotor behavior tended to be suppressed on the days of amperozide pairings, elevated on the days of vehicle pairings, and elevated on test days. Administration of 20.0 mg/kg but neither 2.0 nor 0.2 mg/kg cocaine produced place preference. Rats exhibited a greater place preference for the chamber paired with 2.0 mg/kg and 20.0 mg/kg but not 0.2 mg/kg cocaine compared to the chamber paired with 5.0 mg/kg amperozide. The results indicate that amperozide is appetitive. The most appetitive dose of amperozide (5.0 mg/kg) is less appetitive than the most appetitive dose of cocaine (20.0 mg/kg). More research is needed before conclusions regarding the degree of abuse potential for amperozide can be made. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Response requirements and unit dose modify the effects of GBR 12909 on cocaine-maintained behavior.

Previous studies found that GBR 12909 can decrease cocaine-maintained responding at doses that do not affect food-maintained responding. In this study, the effects of GBR 12909 (0.3–3.0 mg/kg) were further examined by varying the response requirement and unit dose of cocaine. Rhesus monkeys earned food or cocaine under a multiple fixed-ratio (FR) schedule. The FR for food was always 30, but the FR for cocaine was varied from 10–130 and the unit dose was varied from 5.6–56.0 μg/kg per injection. Doses of GBR 12909 were tested in an ascending order, for 5 consecutive sessions each. GBR 12909 selectively decreased cocaine maintained responding in all monkeys in at least 1 condition. These effects were enhanced with large response requirements and/or small unit doses. The results demonstrate that environmental variables can influence the selectivity of GBR 12909's effects and contribute to a growing debate concerning the evaluation of potential pharmacotherapies for drug abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Drug-induced reinstatement to heroin and cocaine seeking: A rodent model of relapse in polydrug use.

The authors investigated several features of polydrug use in rats. Heroin and cocaine were self-administered following responses on different levers, with only 1 drug and 1 lever available on alternate days of training. Four doses of each drug (heroin: 25, 50, 100, and 200 μg/kg/infusion; cocaine: 0.25, 0.5, 1, and 2 mg/kg/infusion) were tested, and each rat was exposed to a single dose combination. Rats readily developed drug-specific and dose-related responding. During extinction, rats displayed a significant bias for responding on the cocaine-associated lever. Priming injections of either cocaine (20 mg/kg) or heroin (0.25 mg/kg) reinstated responding that was selective for the lever previously associated with each drug These results suggest that in this type of polydrug use, drugs have the capacity to activate drug-seeking behavior selectively oriented toward stimuli previously associated with their administration. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evaluation of the reinforcing and discriminative stimulus effects of cocaine in combination with (+)-AJ76 or clozapine

Because self-administration and discrimination of a drug by animals correlate with its abuse and subjective effects in humans, interventions that modify the reinforcing and discriminative stimulus effects of the drug may be useful in the treatment of its abuse. The present study was designed to evaluate the effects of the putative dopamine autoreceptor antagonist (+)-AJ76 (AJ) or the atypical antipsychotic clozapine (CLZ) on the reinforcing and discriminative stimulus effects of cocaine in monkeys. One group of rhesus monkeys (n = 6) was allowed to self-administer cocaine (0.03 or 0.1 mg/kg/injection i.v. fixed-ratio 10, 2 hr/day). A second group of monkeys (n = 5) was trained to discriminate cocaine (0.2 or 0.4 mg/kg i.m., 10 min presession) from saline in a two lever, food-reinforced, drug discrimination paradigm. When behavior was stable, AJ or CLZ was administered i.m., 15 or 30 min presession. Intermediate doses of both compounds (1.0-3.0 mg/kg of AJ; 0.3-1.0 mg/kg of CLZ) increased cocaine self-administration, while responding remained evenly distributed over the session. A higher dose of CLZ decreased cocaine self-administration in an apparently nonspecific manner. When combined with saline, partial substitution for cocaine was seen in one of three monkeys with AJ and in none with CLZ. In combination with the training dose of cocaine in the discrimination experiment, both AJ and CLZ decreased drug appropriate responding by at least 50% in two of four monkeys, but had little or no effect in the other monkeys up to doses that completely suppressed lever pressing (6.4 mg/kg of AJ; 3.2 mg/kg of CLZ). Taken together, the present findings suggest that any blockade of the reinforcing and discriminative stimulus effects of cocaine by AJ and CLZ was, at best, partial. Furthermore, the stimulant effects of AJ observed in rats were not prominent in monkeys.     

Buprenorphine-induced alterations of cocaine's reinforcing effects in rhesus monkey: a dose-response analysis

Buprenorphine reduces cocaine self-administration by rhesus monkeys, opiate- and cocaine-dependent men and polydrug abusers, but the mechanisms underlying these cocaine-opiate interactions are not well understood. In the present study, the effects of daily placebo or buprenorphine (0.1, 0.3 and 1.0 mg/kg) treatment on cocaine self-administration (0.001-0.3 mg/kg/inject) were examined in five cocaine-experienced rhesus monkeys. Saline and each of six cocaine doses were available in an irregular order. Responding for cocaine (or saline) and food was maintained on a second order FR4 (VR 16:5) schedule of reinforcement. During placebo treatment, the daily number of cocaine injections increased as the unit dose was increased and then decreased at higher doses. Cocaine doses that maintained the highest rates of responding during placebo treatment were more resistant to buprenorphine's effects. The typical increase in response rate during the first five cocaine injections of a session also was attenuated by buprenorphine. The ascending limb of the cocaine dose-response curve was shifted downward and approximately one log unit to the right during low-dose buprenorphine treatment (0.1 mg/kg/day). In contrast, individual response rates for food pellets were unaffected. We conclude that buprenorphine selectively decreases self-administration of some unit doses of cocaine at doses that have minimal effects on food-maintained responding.     

Effects of serotonergic manipulations on cocaine self-administration in rats

Rats were trained to self-administer cocaine (0.5 mg/kg/infusion) and were then pretreated with the 5-HT1A agonist 8-OH-DPAT (0.125, 0.25 or 0.5 mg/kg, SC). 8-OH-DPAT pretreatment produced a decrease in reinforced response rates. When the effect of 8-OH-DPAT (0.5 mg/kg, SC) on responding for a range of cocaine doses was assessed, the drug produced a decrease in response rates when lower doses of cocaine served as the reinforcer. Fluoxetine (10 mg/kg, IV), an indirect 5-HT agonist, also reduced reinforced response rates for a low dose infusion of cocaine. Rates of responding for infusions of higher cocaine doses were not affected by fluoxetine pretreatment during an FR1 schedule of reinforcement. When an FR10 schedule of reinforcement was imposed, reinforced response rates for infusions of higher doses of cocaine were also reduced. Thus, under conditions that produce high rates of responding (low dose infusion or high ratio requirements for an infusion) fluoxetine reduced responding. This effect may be due to the effects at the 5-HT1A receptor, since 8-OH-DPAT produced a similar effect on cocaine self-administration. Given that the effects of these 5-HT agonists are observed only when low doses of cocaine serve as the reinforcer or when task demands are high, it is possible that the suppression of responding reflects an effect that is not specific to the reinforcing impact of cocaine. An alternative explanation for these effects incorporates a concept of unit cost/cocaine infusion that allows for direct comparison across studies that employ different reinforcement schedules.     

Effects of phentermine on responding maintained under multiple fixed-ratio schedules of food and cocaine presentation in the rhesus monkey

Drugs that decrease drug-maintained responding at doses that do not decrease other behaviors in animals may be suitable candidates for development as medications to treat drug abuse in humans. The present study examined whether this effect could be obtained with phentermine, a drug that has been reported to decrease cocaine intake in humans. Rhesus monkeys were trained under multiple fixed-ratio 30-response schedules of food and i.v. cocaine delivery. Phentermine was always given as a slow, i.v. infusion. Acute treatment with phentermine (0.3-10 mg/kg) decreased cocaine-maintained responding at doses that did not decrease, or decreased less, food-maintained responding for each of three unit doses of cocaine (10-100 microg/kg/injection). Subacute treatment with phentermine (3 or 5.6 mg/kg, daily) also decreased cocaine-maintained responding more than food-maintained responding. After subacute treatment was terminated, rates of cocaine-maintained responding generally recovered to levels comparable to those seen during untreated control sessions. Phentermine (0.3-3 mg/kg) did not generally increase responding associated with a very low (1 microg/kg/injection) unit dose of cocaine, suggesting that the decrease in cocaine-maintained responding at higher unit doses was not the result of a leftward shift in the cocaine unit dose-effect function. Phentermine (0.1-3 mg/kg) decreased responding maintained by 1-[2-[bis(4-fluorophenyl) methoxy]ethyl]-4-[3-phenylpropyl] piperazine (GBR 12909) (30 microg/kg/injection) at doses similar to those that decreased food-maintained responding. These results show that phentermine is effective in decreasing cocaine self-administration and suggest that it may be an effective medication for cocaine abuse.     

Cocaine exposure causes long-term increases in impulsive choice.

In this study, the authors examined the long-term effects of prior exposure to cocaine on a delay-discounting task commonly used to measure impulsive choice. Male Long-Evans rats received daily intraperitoneal injections of 30 mg/kg cocaine HCl or saline for 14 days. Following 3 weeks of withdrawal, rats began training. On each trial, rats were given a choice between 2 levers. A press on 1 lever resulted in immediate delivery of a single 45-mg food pellet, and a press on the other resulted in delivery of 4 pellets after a delay period. Impulsive choice was defined as preference for the small immediate over the large delayed reward. Three months after treatment, cocaine-exposed rats displayed increased impulsive choice behavior. They also showed less anticipatory responding (entries into the food trough) during the delays prior to reward delivery, indicating that the enhanced impulsive choice in these rats may be related to deficits in bridging the delay between response and reward. These data demonstrate that cocaine exposure can cause enduring increases in impulsive choice behavior, consistent with observations in human subjects with drug addictions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential control over drug-seeking behavior by drug-associated conditioned reinforcers and discriminative stimuli predictive of drug availability.

Conditioned stimuli (CSs) can control behavior either by activating responses when presented noncontingently or through their ability to maintain responding when presented contingently, that is, as conditioned reinforcers. In the present study, the extent to which drug-seeking behavior could be subject to these different types of stimulus control was studied by presenting to rats CSs that were either paired with each drug infusion or presented as discriminative stimuli (DSs) signaling the availability of drug. It was found that stimuli paired with either cocaine or heroin infusions increased drug seeking when presented contingent on responding, but not when presented noncontingently. By contrast, DSs that signaled cocaine availability increased drug seeking when presented either noncontingently or contingently. These results suggest that drug-seeking behavior can be influenced differentially by CSs and that conditioned reinforcers are especially important for maintaining prolonged sequences of drug-seeking behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of progesterone on the reinstatement of cocaine-seeking behavior in female rats.

Estradiol benzoate (EB) facilitates the acquisition and reinstatement of cocaine-seeking behavior when administered to ovariectomized (OVX) rats. In contrast, progesterone (P) decreases acquisition of cocaine self-administration, but the effects of P on the reinstatement of drug seeking are not known. The purpose of the present study was to compare the effects of EB and P on the reinstatement of cocaine-seeking behavior in female rats. Rats received either OVX or sham surgery (SH) and were trained to lever press for intravenous cocaine infusions (0.4 mg/kg) under a fixed ratio 1, 20-s time-out schedule during daily 2-hr sessions. After 14 days of stable responding, saline replaced cocaine, and a 21-day extinction period began. After extinction, rats were separated into 5 treatment groups (OVX+EB, OVX+EB+P, OVX+vehicle [VEH], SH+P, or SH+VEH), and VEH, EB, or EB+P was administered 30 min prior to each session for 5 days. After 3 days of hormone treatment, rats received a saline or cocaine (10 mg/kg) injection, and reinstatement of lever responding was assessed. Reinstatement responding in the OVX+EB group was greater relative to the OVX+EB+P, SH+P, and OVX+VEH groups, which had low levels of cocaine-primed responding. The SH+VEH and OVX+EB groups displayed similar high levels of cocaine-elicited reinstatement. The suppression of cocaine-induced reinstatement following P treatment suggests a role for P in the prevention of relapse to cocaine self-administration in female cocaine users. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Regulation of intravenously self-administered nicotine in rats.

Ten male Wistar rats had access to 9 doses of nicotine (0.01–0.10 mg/kg iv) during daily 5-hr sessions. Once responding for nicotine stabilized, nicotine infusions were replaced with either cocaine infusions (0.0–2.4 mg/kg) or saline infusions. Saline substitution results indicate that nicotine functioned as a reinforcer. Regulation of nicotine intake was compared with that of cocaine by obtaining the correlation between mean interdose interval and preceding dose size. Results reveal that although this correlation was significant for both nicotine and cocaine self-administration, nicotine self-administration was less precisely regulated than cocaine self-administration. This procedure suggests that there are differences in regulation among self-administered drugs and that it may serve as a useful baseline for studying differences in vulnerability to drug abuse and potential treatment strategies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The microcirculation and survival of experimental flow-through venous flaps

We assessed the effects of chronic (21 day) administration of antipsychotic drugs on the density of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor in rat brain. We used two typical antipsychotic drugs, haloperidol and pimozide, and two atypical antipsychotic drugs, risperidone and clozapine. Antipsychotic drugs as a group significantly elevated the density of the AMPA receptor measured with an AMPA receptor agonist ([3H]AMPA), but not with an AMPA receptor antagonist, 6-cyano-7-nitro-quinoxaline-2,3-dione ([3H]CNQX). In all regions studied, the magnitude of the increase seen with chronic typical antipsychotic drugs was significantly greater than that seen with chronic atypical antipsychotic drugs. In frontal cortex and striatum, typical antipsychotics but not atypical antipsychotics elevated AMPA receptor binding over control. These findings suggest that antipsychotic drugs alter the agonist affinity of the AMPA receptor without altering the number of AMPA receptors. Typical antipsychotic drugs may be more potent in this effect than atypical antipsychotic drugs, especially in critical corticostriatal circuits.     

Effects of dopamine reuptake inhibitors on food- and cocaine-maintained responding: I. Dependence on unit dose of cocaine.

The effects of the high-affinity dopamine reuptake inhibitor, GBR 12909, were studied on responding maintained under multiple fixed ratio (FR) schedules of food and cocaine delivery in rhesus monkeys (Macaca mulatta). GBR 12909 decreased rates of responding maintained by both events in a dose-related manner, however, large decreases in cocaine-maintained responding could be obtained with doses of GBR 12909 that had little effect on food-maintained responding. This behavioral selective effect of GBR 12909 on cocaine-maintained responding was inversely related to the unit dose of cocaine. When responding was maintained by low doses of cocaine, GBR 12909 (1 mg/kg) decreased cocaine-maintained responding almost completely. When responding was maintained by the highest dose, the same dose of GBR 12909 had little effect on responding. To the extent that higher doses of cocaine may be expected to be more reinforcing, the current results suggest that the effect of GBR 12909 on cocaine-maintained responding was determined by the reinforcing efficacy of the unit dose of cocaine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Experiences of 23 patients > or = 90 years of age treated with radiation therapy

Previous studies showed that the 5-HT2 receptor antagonist, amperozide, is somewhat more potent than the opiate antagonist, naltrexone, in reducing alcohol drinking in high alcohol-preferring (P) rats. The purpose of this study was to determine in the P rat whether the effect of either drug could be due, in part, to an alteration in gustatory function. In an unlimited, 24-h free choice paradigm, P rats were offered water simultaneously with either a highly palatable 0.1% saccharin solution or a 1:4 dilution of Nestlé Sweet Success chocolate drink. Throughout all phases of the study, the P rats always consumed significantly greater volumes of the chocolate drink than of the saccharin solution, i.e., 526 ml/kg vs. 181 ml/kg, respectively. Successive 12-day experimental periods consisted of three phases: a 4-day predrug control interval; 4 days of administration of saline control vehicle or either drug; and a final 4 day postdrug interval. In a counterbalance design, saline, amperozide (1.0 or 5.0 mg/kg) or naltrexone (2.5 or 5.0 mg/kg) was administered subcutaneously twice daily at 1600 and 2200 h for 4 days. Amperozide and naltrexone significantly reduced the drinking of chocolate in a dose-dependent manner. Conversely, only the two higher doses of amperozide and naltrexone decreased the intake of saccharin significantly. Thus, these findings suggest that different populations of central serotonin and opioid receptors concurrently underpin, in part, the preferences for both palatable and/or nutrient fluids. Finally, because both the opiate and 5-HT2A antagonists reduce the ingestion of saccharin and chocolate solutions differentially, it is apparent that preferences for alternative palatable fluids should be examined when candidate drugs are screened for suppressing alcohol drinking and ultimately the treatment of alcohol abuse.     

Antagonism at delta opioid receptors blocks cocaine's, but not morphine's, enhancement of responding for intracranial stimulation.

Rats were fixed with a chronically indwelling bipolar electrode for direct electrical stimulation of the medial forebrain bundle as it courses through the lateral hypothalamus. In Experiment 1, the rats were trained to self-stimulate (i.e., lever press) at each of 3 intensities of intracranial stimulation (ICS) for 10 min daily. In Experiment 2, only 2 intensities were offered. After stable daily rates of responding for each intensity of ICS were established, rats received either cocaine (5 or 10 mg/kg) or morphine (4 mg/kg) daily. Both cocaine and morphine significantly increased rates of responding. Naltrindole (NTI; 10 mg/kg) reduced rats' rates of responding under cocaine to those observed under vehicle. NTI had very little impact on morphine's effects. These data support the conclusion that selective 8 opioid receptor antagonists may be useful for treating cocaine addiction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)