Amphetamine sensitization: Nonassociative and associative components.

[Correction Notice: An erratum for this article was reported in Vol 117(6) of Behavioral Neuroscience (see record 2007-16849-001). The institutional affiliation for Ying-Chou Wang is incomplete. The correct affiliation is Ching Kuo Institute of Management and Health and National Chung Cheng University.] Rats, pretreated with amphetamine (AMPH, 1 mg/kg) or saline for 2 weeks, were challenged with AMPH (0.5 mg/kg) or saline following 1 week of abstinence, and locomotion was measured. In Experiments 1 and 2, the pretreatment occurred in various contexts (home cage, novel box, test box). Sensitization was observed only when pretreatment context and test context were the same; a context switch abolished sensitization. When rats anesthetized with chloral hydrate were pretreated with AMPH, sensitization was completely dependent on the pretreatment, but independent of context. This "zero context" condition isolated the basal level of excitation attributable to unconditioned neural change to determine the role of contextual input to be a modulator that enhances or inhibits sensitization. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Time-dependent effects of repeated amphetamine treatment on norepinephrine in the hypothalamus and hippocampus assessed with in vivo microdialysis

The effects of repeated amphetamine (AMPH) pretreatment on norepinephrine (NE) neurotransmission in the hypothalamus and hippocampus were assessed using in vivo microdialysis. Rats were pretreated with either saline or an escalating-dose AMPH regimen (1-->10 mg/kg) over 10 consecutive days, and then were withdrawn from AMPH for either 1 day or 30 days, at which time the animals underwent two consecutive days of testing. As expected, repeated treatment with AMPH resulted in time-dependent changes in both spontaneous locomotor activity and in the psychomotor response to a subsequent challenge injection of AMPH. In addition, repeated exposure to AMPH resulted in time-dependent and regionally-specific changes in the basal concentrations of NE in dialysate, and in the NE response to an AMPH challenge. For example, AMPH pretreatment produced a persistent (at least one month) increase in the basal concentration of NE in the hippocampus, but not the hypothalamus, although the response to an AMPH challenge was altered in both structures. It is suggested that AMPH treatment produces adaptations in NE systems that far outlast the acute effects of the drug, and that these may contribute to both transient and more persistent behavioral sequelae associated with the discontinuation of chronic AMPH use.     

Effects of repeated methylphenidate treatment in the young rat: Sensitization of both locomotor activity and stereotyped sniffing.

The behavioral effects of repeated methylphenidate (MPH) treatment were assessed in young rats. In 4 experiments, rats (starting at Postnatal Day 10 or 16) were pretreated on 5 consecutive days with saline or MPH (2.5–20.0 mg/kg ip). Sensitization was assessed after 1 or 7 abstinence days, with rats receiving a test day challenge injection of either a low dose of MPH (2.5 mg/kg) or the same dose of MPH as given during pretreatment. Results show that a test day injection of 2.5 mg/kg MPH produced a sensitized locomotor response in rats pretreated with 2.5–20.0 mg/kg MPH. This MPH-induced locomotor sensitization was evident only after 1 abstinence day. Various pretreatment doses of MPH (5, 10, 15, or 20 mg/kg) were capable of sensitizing the stereotyped sniffing of young rats, but only rats pretreated and tested with the highest dose (20 mg/kg) of MPH showed an augmented stereotyped sniffing response that was still robust after 7 abstinence days. Results indicate that young rats are capable of exhibiting sensitization after an extended abstinence period, which contrasts with previous research suggesting that psychostimulant treatment does not produce long-term sensitization in young rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Purinoceptor modulation of noradrenaline release in rat tail artery: tonic modulation mediated by inhibitory P2Y- and facilitatory A2A-purinoceptors

Repeated administration of amphetamine-like stimulants to rats results in enhanced behavioral responsiveness to subsequent administration of these drugs. Recent evidence suggests corticosterone may play a role in the development of sensitization perhaps through the down-regulation of glucocorticoid receptor (GR). To test this hypothesis further we examined the effects of five daily injections of amphetamine (AMPH) (2.5 mg/kg) on GR mRNA of adult Sprague-Dawley rats. Two other groups received saline for 4 days and then either saline or AMPH on the fifth day. All animals were killed 24 h after the last treatment and in situ hybridization was performed with an antisense mRNA GR probe. Quantification of hippocampal GR was accomplished by computer analysis of digitized images of CA1 and dentate gyrus. Acute AMPH produced a significant up-regulation of GR mRNA in CA1 and a nonsignificant trend towards up-regulation in the dentate gyrus. Repeated exposure to AMPH resulted in a significant down-regulation in CA1, and a nonsignificant trend towards down-regulation in dentate gyrus. These data support a role for hippocampal GR mRNA in the development of behavioral sensitization.     

"Effects of chronic and acute cocaine treatment on the onset of maternal behavior and aggression in Sprague-Dawley rats": Correction.

Reports an error in the original article by J. M. Johns et al (Behavioral Neuroscience, 1994[Feb], Vol 108[1], 107–212). On page 108, in the Results, Maternal Behavior, the phrase in parentheses, "(8 min to crouch for 8 min or more of 30 min)' should read: "(6 min to crouch for 8 min or more of 30 min).' On page 109, the label on the upper right panel of Figure 1, "Percent That Crouch in 8 Minutes,' should read: "Percent That Crouch in 6 Minutes.' (The following abstract of this article originally appeared in record 1994-24731-001.) Pregnant rats (N?=?17) were treated either throughout gestation (Gestational Day 1–20) with 30 mg/kg per day (chronic cocaine) or with 1 15-mg/kg dose immediately following parturition (acute cocaine). Chronic and acute cocaine treatment delayed or diminished the postpartum onset of some components of maternal behavior, and chronically treated dams were significantly more aggressive toward a male intruder than acute cocaine-treated or saline-treated dams. Cocaine increased the latency to crouch over pups and decreased crouch duration during a 30-min observation period that immediately followed parturition. Latencies to nest build were also longer in more chronic cocaine-treated dams than in saline controls.… (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selenium lethality: role of glutathione and metallothionein

Male Sprague-Dawley rats (200-300 g) were pretreated (i.p.) with diethylmaleate (DEM; 3.1 mmol/kg) or propylene glycol (PG). After 1 h, three PG and three DEM groups received saline or sodium selenite (Se: 0.8 or 1.6 mg/kg) i.p. Eighty to one hundred percent mortality occurred within 3 h after Se in DEM-pretreated groups. Except for one PG and one DEM group, which were sacrificed after 1 h, the remaining groups received saline or Se (1.6 mg/kg) 25 h after pretreatment. No mortality occurred within 3 h after Se. Liver and kidney GSH decreased at 1 h, while liver MT increased at 28 h. The changes are related to Se-induced lethality.     

"Team negotiation: An examination of integrative and distributive bargaining": Correction.

Reports an error in "Team negotiation: An examination of integrative and distributive bargaining" by Leigh Thompson, Erika Peterson and Susan E. Brodt (Journal of Personality and Social Psychology, 1996[Jan], Vol 70[1], 66-78). Susan E. Brodt's department affiliation was listed incorrectly on p. 66. Her correct affiliation is The Fuqua School of Business, Duke University. (The following abstract of the original article appeared in record 1996-01707-006.) Two experiments compared the effectiveness of team and solo negotiators in integrative and distributive bargaining. When at least 1 party to a negotiation was a team, joint profit increased. Teams, more than solos, developed mutually beneficial trade-offs among issues and discovered compatible interests. The presence of at least 1 team increased information exchange and accuracy in judgments about the other party's interests in comparison with solo negotiations. The belief by both teams and solos that teams have a relative advantage over solo opponents was not supported by actual outcomes. Unexpectedly, neither private meetings nor friendships among team members improved the team's advantage. Teams of friends made less accurate judgments and reached fewer integrative agreements compared to teams of nonfriends. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Depletion of dopamine in the nucleus accumbens prevents the generation of locomotion by metabotropic glutamate receptor activation

The contribution of dopamine (DA) to the locomotion elicited by activation of nucleus accumbens (NAcc) metabotropic glutamate receptors (mGluRs) was investigated in the rat. Different groups of rats were pretreated with bilateral microinjections of either 6-hydroxydopamine (6-OHDA) or its vehicle into the NAcc and, on separate tests starting 10 days later, were tested for locomotion following microinjections (into the same site) of saline, the mGluR agonist, 1-aminocyclopentane-trans-1,3-dicarboxylic acid [(1S, 3R)-ACPD, 0.5 nmol/side] and amphetamine (AMPH, 6.8 nmol/side). DA levels at the microinjection sites were significantly depleted in 6-OHDA-treated rats (42-99% depletions compared to control values obtained in vehicle-treated rats). In contrast to the increased locomotion observed in non-lesioned animals, rats pretreated with 6-OHDA showed no increase in locomotor activity in response to (1S, 3R)-ACPD or AMPH when these were microinjected into the NAcc. The two groups of rats were indistinguishable when tested following NAcc saline. These findings suggest that, as with AMPH, enhanced locomotion produced by NAcc mGluR activation is dependent on intact DA neurotransmission in this site.     

One-trial cocaine-induced behavioral sensitization in preweanling rats: Role of contextual stimuli.

Using a one-trial procedure, preweanling rats exhibit robust sensitization regardless of whether drug pretreatment and testing occur in the same or different environments. The purpose of the present study was to determine whether one-trial context-specific and context-independent sensitization of preweanling rats could be dissociated by varying the pretreatment dose of cocaine, by varying the pretreatment drug, or by minimizing interoceptive cues. In Experiments 1a and 1b, rats were pretreated with a broad dose range of cocaine (0–40 mg/kg) before placement in a novel activity chamber or the home cage. In Experiment 2, rats were pretreated with a locomotor-enhancing drug (e.g., methylphenidate, U50,488, or MK-801) before placement in a novel activity or anesthesia chamber. In Experiment 3, rats were anesthetized with isoflurane before cocaine administration to minimize the effects of interoceptive and injection cues. In all experiments, rats were challenged with cocaine on the test day (24 hr later), with locomotion being measured in activity chambers. Results showed that (a) the pretreatment dose of cocaine (10–40 mg/kg) did not differentially affect context-specific and context-independent sensitization; (b) cross-sensitization between methylphenidate and cocaine was observed in the context-specific condition, but not when using a context-independent procedure; and (c) sensitization was evident if injection and interoceptive cues were minimized. One possibility is that associative processes do not modulate the one-trial sensitization of preweanling rats. Alternatively, “unitization” may cause preweanling rats to treat the different environments as equivalent, thus permitting robust sensitization even when drug pretreatment and testing occur in different environments. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"Taste reactivity responses elicited by cocaine-, phencyclidine-, and methamphetamine-paired sucrose solutions": Correction to Parker.

Reports an error in "Taste reactivity responses elicited by cocaine-, phencyclidine-, and methamphetamine-paired sucrose solutions" by Linda A. Parker (Behavioral Neuroscience, 1993[Feb], Vol 107[1], 118-129). Table 1, on page 119, contains two errors. In the first section, the dose/route for the agent nicotine should read as follows: 1.2-2.0 mg/kg sc. In the second section, the dose/route for the agent morphine should read as follows: 2-80 mg/kg ip. Also, on page 121, paragraph 3, line 14, the parenthetical information after 40 mg/kg cocaine should read (40C; 2 × 20 mg/kg/3 cc). (The following abstract of the original article appeared in record 1993-24959-001.) The nature of flavor–drug associations produced by a range of doses of the reinforcing agents cocaine (5, 10, 15, 20, or 40 mg/kg, sc), phencyclidine (0.5, 2, 10, or 20 mg/kg, sc), and methamphetamine (2, 5, or 10 mg/kg, ip) were assessed by the taste reactivity (TR) test and the conditioned taste avoidance (CTA) test. Even at the highest doses tested, none of the agents produced aversive TR responding. At doses that produced equivalent-strength CTA, lithium did establish aversive TR responding. Results provide evidence that drugs that serve as reinforcers in other paradigms produce conditioned flavor avoidance that is not motivated by a conditioned dislike for the flavor. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Opioid Craving and Seeking Behavior in Physically Dependent Volunteers: Effects of Acute Withdrawal and Drug Reinforcement Opportunity.

This study examined whether acute opioid withdrawal and drug reinforcement opportunity increase opioid craving and seeking behavior. The author used a 3 × 2 within-subject randomized crossover design to assess craving and operant behavioral effects of 3 pretreatments (naloxone 0.1 mg/70 kg, fentanyl 0.75 mg/70 kg, or saline iv) and drug or money reinforcement opportunity in 8 methadone-maintained volunteers. Each pretreatment was paired with response-contingent (15 × fixed-ratio 100) delivery of drug (fentanyl 1.5 mg/70 kg iv) and money (rated equivalent of fentanyl) in different sessions. Naloxone significantly increased opioid craving, withdrawal signs, and symptoms, but not operant behavior, relative to saline and fentanyl pretreatment. However, drug versus money reinforcement opportunity did not significantly increase opioid craving or seeking behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"Acceptability and availability of harm-reduction interventions for drug abuse in American substance abuse treatment agencies": Correction to Rosenberg and Phillips (2003).

Reports an error in "Acceptability and availability of harm-reduction interventions for drug abuse in American substance abuse treatment agencies" by Harold Rosenberg and Kristina T. Phillips (Psychology of Addictive Behaviors, 2003[Sep], Vol 17[3], 203-210). On page 208, the first sentence in the note of Table 4 incorrectly reads as follows: "Numbers in parentheses are ns of respondents who provided an 'other' reason for this specific intervention." The sentence should read as follows: "Numbers in parentheses are ns of respondents whose agencies do not offer this intervention." (The following abstract of the original article appeared in record 2003-07737-003.) This study assessed acceptability, availability, and reasons for nonavailability of interventions designed to prevent drug use related harm by substituting pharmaceuticals for illicit drugs; facilitating detoxification; and reducing the occurrence of HIV transmission, relapse, and opiate overdose. A survey was mailed to a sample of 500 randomly selected American substance abuse treatment agencies. Of 435 potentially eligible respondents, 222 (51%) returned usable data. A subset of interventions--including harm reduction education, cue exposure therapy, needle exchange, substitute opiate prescribing, various detoxification regimes, and complementary therapies--were rated as somewhat or completely acceptable by 50% or more of the respondents. Regardless of their acceptability, listed interventions were generally not available from responding agencies; respondents typically attributed unavailability to lack of resources and inconsistency of an intervention with agency philosophy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"An historical note on Darwin and nonhuman drug self-administration": Clarification to Higgins (2003).

Reports a clarification in "An historical note on Darwin and nonhuman drug self-administration" by Stephen T. Higgins (Experimental and Clinical Psychopharmacology, 2003[Nov], Vol 11[4], 317). It is noted that Charles R. Schuster served as the Action Editor for this article. (The following abstract of the original article appeared in record 2003-09137-009.) This note brings to the attention of readers a quote from Charles Darwin on the scientific implications of nonhuman drug self-administration. The quote is from The descent of man; and Selection in relation to sex (2nd ed.; C. Darwin, 1874/1998). Consistent with Darwin's prescience in many areas of science, he discerned potential scientific importance in voluntary nonhuman drug self-administration almost a century before that potential was realized in any substantive or systematic manner. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Verapamil protection against mercuric chloride-induced renal glomerular injury in rats

We have examined the effects of the calcium channel blocker verapamil on the renal glomerular structural damage produced by mercuric chloride in rats. Verapamil (75 micrograms/kg body wt iv) was administered 30 min prior to mercuric chloride injection (HgCl2, 5 mg/kg body wt sc). Verapamil prevented the glomerular proteinuria observed in HgCl2-treated rats. Isolated glomeruli from mercury-treated rats 1 h after injection presented a diminished cross-sectional area as compared with control glomeruli (control [micron2], 26,310 +/- 2545; HgCl2 [micron2], 18,474 +/- 1828) and increased glomerular calcium content (control, 23 +/- 6 nmol/mg protein; HgCl2, 43 +/- 7 nmol/mg protein). Verapamil pretreatment prevented glomerular cross-sectional area (GCSA) diminution and glomerular calcium content rise (GCSA [micron2] Vp + Hg, 28,281 +/- 4654, Ca2+ [nmol/mg protein] Vp + Hg, 18 +/- 5). Renal sections prepared for immunohistochemical detection and histochemical analysis showed increased deposits of fibronectin and lipids and enhanced cellularity in glomerular structures from HgCl2-treated rats. Renal sections from animals pretreated with verapamil showed fibronectin and lipid contents not different from control sections and their histological studies did not show any changes when compared with control. Verapamil pretreatment also protected glomeruli from enhanced leukocyte content (myeloperoxidase activity/mg protein): control, 59 +/- 7; HgCl2, 134 +/- 10; Vp + Hg, 79 +/- 11). HgCl2 also contracts GCSA in vitro; Vp prevented this GCSA diminution. The results described in this study indicate that mercuric chloride nephrotoxicity may be associated not only with changes in renal glomerular haemodynamics, but also with a direct effect on glomerular cells.     

Dual-earner families: the importance of work stress and family stress for psychological well-being

The effect of neonatal hippocampal lesions on behavioral sensitivity to amphetamine (AMPH) and dopamine (DA) release in the nucleus accumbens (NAc) were examined. The ventral hippocampus was damaged bilaterally by ibotenic acid on postnatal day 7 (PD7). Spontaneous exploration and AMPH-stimulated locomotor activity were examined on postnatal day 35 (PD35) and day 56 (PD56). Extracellular DA, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were sampled using in vivo microdialysis while simultaneously AMPH-stimulated locomotion was examined in freely moving rats on PD56. Spontaneous exploration increased in rats with hippocampal lesions relative to controls on PD56 but not PD35. AMPH (0, 0.187, 0.375, 0.75, 1.5, and 3 mg/kg) enhanced locomotion dose-dependently in both control and lesioned groups. Locomotor activity was higher in lesioned rats than controls following AMPH at the dose of 0.75 mg/kg on PD35 and at the doses of 1.5 and 3.0 mg/kg on PD56. The basal level of DA in the NAc was not different between the hippocampal and control groups. AMPH (1.5 mg/kg) induced hyperlocomotion in lesioned rats relative to controls. DA release in the NAc for both groups was enhanced following injections of AMPH. However, neonatal hippocampal lesions had no further enhancement on AMPH-stimulated release of DA as compared to the control group. The levels of DOPAC and HVA in the NAc were altered by AMPH but not lesions. The level of 5-HIAA was not influenced by either lesions or AMPH. The results of neonatal lesion-induced hyperlocomotion suggest that an emergence of behavioral hyperresponsiveness to AMPH was dependent on an interaction of lesions, age of examination, and dose of the drug. A dissociation between the effect of AMPH on lesion-enhanced hyperlocomotion and a lack of a lesion-enhanced DA release in the NAc suggest that presynaptic release of DA had no major contribution to lesion-enhanced DA transmission in the mesolimbic DA system.     

Evidence for the involvement of phospholipase A2 mechanisms in the development of stimulant sensitization

Evidence suggests that phospholipase A2 (PLA2) activation is involved in numerous neuroplastic phenomena, including long-term potentiation. Considering the pharmacological similarities between long-term potentiation and stimulant sensitization, it seems possible that PLA2 inhibition activity also might have a role in the induction of stimulant sensitization. In this study, we have investigated whether PLA2 inhibition, by quinacrine, has any effects on stimulant-induced behavioral sensitization. Both locomotor and stereotypic behavioral sensitization were dose-dependently blocked in rats pretreated with quinacrine (8-25 mg/kg i.p.) 15 min before cocaine (30 mg/kg i.p.), when tested with cocaine (15 mg/kg i.p) 72 hr later. Similar results also were found with d-amphetamine (2 mg/kg i.p.) sensitization using a 10-day treatment regimen with testing on day 11. The ability of PLA2 activation, by melittin, to produce cocaine sensitization also was tested. Local injections of melittin (0.1 microgram/0.4 microliter) into the ventral tegmental area sensitized the subsequent stimulation of locomotor activity, stereotypy and nucleus accumbens dopamine release by cocaine, when tested 72 hr later. Local injections of melittin (0.1-1.0 microgram/0.8 microliter) into the nucleus accumbens had a moderate sensitizing effect on locomotion. Quinacrine (16 mg/kg) pretreatment 45 min before intraventral tegmental area melittin injection significantly decreased melittin-induced sensitization of the locomotor and stereotypy response to cocaine. These results indicate that PLA2 activation may play a role in the induction of stimulant sensitization. It is proposed that PLA2 activity in mesolimbic dopamine neurons, at the level of the cell bodies and perhaps the nerve terminals, is involved in the biochemical mechanisms mediating the development of stimulant sensitization.     

Sex differences in nicotine sensitization and conditioned hyperactivity in adolescent rats neonatally treated with quinpirole: Role of D2 and D3 receptor subtypes.

Neonatal quinpirole treatment in rats produces increased sensitivity of dopamine D2-like receptors throughout the animal’s lifetime, referred to as D2 priming. There is little information on the effects of nicotine in adolescent rats, especially in a model that has clinical relevance to psychosis where increased D2 receptor sensitivity is common. Male and female rats were treated with quinpirole (1 mg/kg) or saline from postnatal (P) day 1–P21, given nicotine (0.5 mg/kg) or saline from P33 through P49, and placed into a locomotor arena for behavioral testing. Nicotine or saline treatment was preceded by the D2-like receptor antagonist eticlopride, D3 antagonist nafadotride, or saline. Conditioned hyperactivity was analyzed on P50 in the same context in a drug-free test. In females, D2 priming increased the locomotor response to acute nicotine, but did not affect subsequent nicotine sensitization, and only non–D2-primed females demonstrated conditioned hyperactivity. Eticlopride and nafadotride blocked behavioral sensitization, although nafadotride was more effective at blocking nicotine-conditioned hyperactivity in females. In males, D? priming enhanced sensitization to nicotine and produced conditioned hyperactivity, which were blocked by eticlopride and nafadotride. These results have implications for psychosis and comorbidity of nicotine abuse in adolescence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Amphetamine reinstates polydipsia induced by chronic exposure to quinpirole, a dopaminergic D2 agonist, in rats

The hypothesis that the combined activation of D1 and D2 dopaminergic receptors is instrumental in inducing amphetamine (AMPH)-mediated hyperdipsia was tested in rats. The D1 agonist SKF-38393 (SKF) and the D2 agonist quinpirole (QNP) were i.p. injected, alone or in combination, to male rats for 10 days. After 2 days of wash-out, a single dose of AMPH (3 mg/kg) was administered. Intake of water and food and diuresis were daily measured at 2, 5 and 24 h. In two further experiments the higher dose of QNP (0.56 mg/kg) was given with two different doses of the D1 antagonist SCH-23390 (SCH), or, respectively, of the peripheral D2 antagonist domperidone (DMP). In a fourth experiment, the possibility that QNP, given alone or in combination with SKF, produces an AMPH-like internal state was evaluated by using a drug-discrimination paradigm. Results show that chronic administration of QNP produced a significant increase of 24 h water intake that was reinstated by AMPH. This QNP effect was only partially prevented by DMP, suggesting a main central mechanism of action. By itself D1 receptor manipulation did not affect water intake, but influenced QNP polydipsia that, accordingly, was enhanced by the lower dose of SKF (0.3 mg/kg) and inhibited by the lower dose of SCH (0.01 mg/kg). In rats trained to discriminate AMPH from solvent, QNP partially generalized for the AMPH stimulus, an effect that was potentiated by SKF. In conclusion, a D1-modulated sensitization of D2 dopaminergic mechanisms is probably involved in AMPH-induced hyperdipsia.     

5-HT3 receptor modulation of behavior during withdrawal from continuous or intermittent cocaine

The present experiments examined alterations in 5-HT3 receptors during withdrawal from continuous or intermittent cocaine. Rats were pretreated with 40 mg/kg/day cocaine for 14 days by either SC injections or osmotic minipumps. The rats were then withdrawn from the pretreatment regimen for 7 days. In Experiment 1, rats received 0-16 mg/kg IP injections of ondansetron, a selective 5-HT3 receptor antagonist. In Experiment 2, the rats received 0-16 mg/kg IP ondansetron in combination with a 15 mg/kg IP injection of cocaine. In Experiment 3, the subjects received 0-16 mg/kg IP injections of ondansetron in combination with a 7.5 mg/kg IP injection of cocaine. Following these injections, the subjects' behavior was rated using the Ellinwood and Balster (18) rating scale. The results of Experiment 1 indicated that ondansetron had no effect on the behavior of the subjects, nor was there a differential effect of pretreatment regimen the effects of ondansetron. The results of Experiment 2 indicated that ondansetron had no effect on cocaine-induced locomotion in the saline control rats, but did have a slight, statistically significant, suppressive effect in the injection rats. In contrast, ondansetron had a robust facilitative effect on cocaine-induced locomotion in the continuous infusion rats. The results of Experiment 3 indicated that ondansetron had no effect on cocaine-induced locomotion in the saline control rats or the cocaine injection pretreatment subjects. In the continuous infusion subjects, ondansetron did have a slight, statistically significant, facilitative effect on cocaine-induced locomotion.(ABSTRACT TRUNCATED AT 250 WORDS)