Dominance hierarchies in leptothorax ants.

The social organization of Leptothorax allardycei is unique among ant species thus far studied. The workers form linear dominance hierarchies characterized by routine displays of dominance, avoidance behavior, and even fighting. The high-ranking ants are favored in liquid food exchange, have greater ovarian development, and produce 20 percent of the eggs.

Comparison of radiofrequency treatment and mechanical debridement of fibrillated cartilage in an equine model.

OBJECTIVE: To compare a radiofrequency energy (RFE) prototype probe to mechanical debridement (MD) and a commercially available RFE system used for chondroplasty in the treatment of an experimentally created partial thickness cartilage lesion in horses. The study design was experimental, randomized complete block, n=8, using fifteen mature ponies. METHODS: Grade 2 to 3 cartilage lesions were prepared in both patellae. After 10 months duration, the injuries were used to study the effects of MD, a commercially available bipolar RFE device (CoVac 50; ArthroCare Corporation) and a prototype monopolar RFE device (Smith & Nephew Endoscopy). Six months after treatment the patellae were examined for chondrocyte viability and cartilage structure. RESULTS: Mean depth of cell death was significantly different among groups (controls, MD

Evaluation of fever in the immediate post-operative period following shoulder arthroplasty.

AIMS: To determine the incidence and timing of post-operative fevers following shoulder arthroplasty and the resulting investigations performed. PATIENTS AND METHODS: A retrospective review was conducted of all patients undergoing shoulder arthroplasty over a nine-year period. The charts of all patients with a post-operative fever (≥ 38.6°C) were reviewed and the results of all investigations were analysed. RESULTS: A total of 2167 cases (in 1911 patients) were included of whom 92 (4.2%) had a documented fever. Obese cases had a significantly greater risk for fever (relative risk 1.53; 95% confidence interval 1.02 to 2.32; p = 0.041). Investigations were performed in 43/92 cases (46.7%), with a diagnosis being made in six cases (6.6% of the total, two of whom had their diagnosis made post-discharge). CONCLUSION: Around one in 25 cases develop a fever following shoulder arthroplasty; most have no infective aetiology. These patients may be being over-investigated; investigations should be performed in patients with persistent fever or on those with an identifiable source of infection on clinical examination. Cite this article: Bone Joint J 2017;99-B:1515-19.

Male size, sperm transfer, and colony fitness in the western harvester ant, Pogonomyrmex occidentalis.

Mating success in the western harvester ant, Pogonomyrmex occidentalis, increases with male size. We tested the hypothesis that increased mating success increases male fitness and the fitness of colonies that make large males by comparing the sperm content of males prior to and at the conclusion of the mating swarm. The number of sperm a male initially possesses is a function of male size, and large males transfer a greater proportion of their sperm than do small males. For colonies, the payoff per unit of investment is an increasing function of male size, and investment in large males is not equivalent to investing in a larger number of small males. Allocation ratios in species that show size variation in reproductives may need to be modified by the individual fitness functions.

Forebrain norepinephrine: role in controlled information processing in the rat.

A series of experiments examined the effects of 6-hydroxydopamine (6-OHDA)-induced depletion of forebrain norepinephrine (NE) on the performance of a visual detection (spatial localization) task. The behavioral paradigm used was an analogue of Leonard's 5-choice serial reaction time task for humans. The 6-OHDA lesion of the dorsal noradrenergic bundle (DNAB) produced a 98% depletion of the NE content in the neocortex, and a much smaller depletion (32%) of the NE content in the hypothalamus. As reported previously, performance of visual discrimination was unaffected by DNAB lesions, even when the discrimination was made more difficult by decreasing the intensity of the visual stimuli. However, the lesion produced a significant decrease in accuracy and a significant increase in omissions when a burst of loud white noise was presented just prior to the onset of the visual discriminanda. Similarly, a significant decrease in discriminative accuracy was produced in the rats with forebrain NE depletion by systemic administration of the psychomotor stimulant, d-amphetamine (0.2 to 0.8 mg/kg). In both of these experiments, the lesion-induced discrimination impairment was not magnified by reducing the brightness of the visual discriminanda, suggesting that the behavioral impairment was not caused by a decreased ability to detect the visual stimuli. In addition, the lesion impaired discriminative accuracy when the visual discriminanda were presented at an unpredictable rate. The implications of these behavioral impairments produced by forebrain NE depletion for theories of catecholamine involvement in attentional processes and arousal are discussed in terms of a possible role for the DNAB in controlled or "effortful" processing.

Dissociable effects of lesions to the dorsal or ventral noradrenergic bundle on the acquisition, performance, and extinction of aversive conditioning.

In six experiments we studied the effects of lesions to either the dorsal or ventral noradrenergic bundle on the acquisition and extinction of the conditioned emotional response (CER) as measured in a conditioned suppression paradigm. Infusions of the neurotoxin 6-hydroxydopamine (6-OHDA) into the trajectory of the dorsal noradrenergic ascending bundle (DNAB) impaired the acquisition of on-the-baseline and off-the-baseline conditioned suppression. The acquisition impairment for on-the-baseline conditioning was also shown to still be present when training did not commence until 8 weeks following central noradrenergic depletion. However, in rats previously trained on the CER, DNAB lesions did not affect performance. There was also a small resistance to extinction following on-, but not off-the-baseline conditioning. The acquisition impairment was shown not to be because of an altered sensitivity to the footshock. In contrast, infusions of 6-OHDA into the ventral noradrenergic ascending bundle (VNAB) had no effect upon the acquisition of the CER in an on-the-baseline procedure, but retarded its extinction to a much greater extent. The results here are discussed in terms of other acquisition deficits shown by rats with DNAB lesions, and with reference to Gray's "anxiety" and Mason's "selective attention" theories of locus coeruleus function.

Low doses of corticotropin-releasing factor potentiate amphetamine-induced stereotyped behavior.

Corticotropin-releasing factor (CRF) is a 41-amino acid polypeptide that is critically involved in the activation of the hypothalamic-pituitary adrenal axis during stress. In addition, it has been suggested that extrahypothalamic CRF may be important in initiating behavioral responses to stressful events. In the present experiment, we examined the effects of central administration of CRF on amphetamine-induced stereotyped behavior. Amphetamine-induced stereotyped behavior has been considered as a behavioral strategy to cope with excessive arousal. Low doses of CRF (0.02 and 0.1 micrograms), administered into the lateral ventricle (ICV), were shown to potentiate amphetamine (4.0 mg/kg; SC)-induced stereotyped behavior, as measured by the Creese and Iversen rating scale and behavioral observations. These low doses of CRF specifically enhanced the tendency for rats to sniff with their heads down 20 min after injection, and induced licking behavior later during testing. In contrast, the rats treated with a higher dose of CRF (0.5 micrograms, ICV) showed more locomotor activity throughout the test, but did not differ from the saline-treated animals in the intensity of amphetamine-induced stereotyped behavior.

Amphetamine impairs the discriminative performance of rats with dorsal noradrenergic bundle lesions on a 5-choice serial reaction time task: new evidence for central dopaminergic-noradrenergic interactions.

A series of experiments examined the effects of lesions of the dorsal noradrenergic bundle (DNAB), induced by 6-hydroxydopamine (6-OHDA), on the behavioural response to systemic and intra-accumbens amphetamine, using a rat analogue of Leonard's 5-choice serial reaction time task for humans. Although the 6-OHDA DNAB lesion produced a profound depletion of cortical noradrenaline (NA) (to around 5% of control levels) it did not impair any aspect of performance on this task. Both systemic and intra-accumbens amphetamine increased behavioural measures of impulsivity of responding, but neither impaired discriminative accuracy in the sham-operated control rats. However, the DNAB lesioned rats did show a discriminative impairment following both low doses of systemic amphetamine, and intra-accumbens amphetamine. The latter effect was antagonised by systemic administration of the specific dopaminergic (DA) antagonist alpha-flupenthixol. The DNAB lesion did not alter the effect of amphetamine on any other behavioural measure, including speed and impulsivity of responding. These results suggest that although DA and NA participate in qualitatively different behavioural processes, the effects of DNAB lesions on attentional processes depend on the level of DA activity within the nucleus accumbens.

Double dissociation between the effects of muscarinic antagonists and benzodiazepine receptor agonists on the acquisition and retention of passive avoidance.

Both muscarinic antagonists, such as scopolamine, and benzodiazepine receptor (BZR) agonists, such as diazepam, produce a reliable impairment in the performance of one trial passive avoidance. Such deficits are frequently interpreted as drug-induced amnesia. However, these deficits could also result from a learning impairment. The present experiments compared the effects of two BZR agonists, lorazepam (0, 0.125, 0.25, and 0.375 mg/kg, IP) and diazepam (0, 0.78, 1.56, and 3.13 mg/kg, IP) with the effects of two muscarinic antagonists, scopolamine (0, 0.6, 0.8 and 1.0 mg/kg, SC) and atropine (0, 15, 30 and 60 mg/kg, IP) on a multiple trial passive avoidance task. In this procedure, the rats were trained with a 5-min inter-trial interval until a learning criterion was achieved. Retention was assessed 24 h later. This enabled the effects of the drugs on the acquisition and the retention of a passive avoidance response to be dissociated. Both atropine and scopolamine produced a marked impairment in the acquisition of the passive avoidance response, but did not impair retention. In contrast, diazepam and lorazepam did not alter the acquisition of a passive avoidance response, but did produce a dose-dependent impairment of retention. These results therefore demonstrate a double dissociation between the effects of muscarinic antagonists and BZR agonists on the acquisition and retention of passive avoidance.

AMPA antagonists differ from NMDA antagonists in their effects on operant DRL and delayed matching to position tasks.

The effects of NBQX (1.56-7.5 mg/kg, i.p.), a competitive antagonist at the AMPA type of glutamate receptor, were studied in two operant behavioural paradigms, differential reinforcement of low response rates (DRL), and delayed matching to position (DMTP), which have been shown to be sensitive to the antagonists of the NMDA type of glutamate receptor. Additionally, the non-competitive AMPA antagonist, GYKI 52466 (7.5-15 mg/kg, i.p.), was studied in the DRL procedure. As a positive control, the non-competitive NMDA antagonist, MK 801 (0.0125-0.1 mg/kg, i.p.) was studied in both procedures. During performance of the DRL schedule, MK 801 increased response rates in a dose dependent manner, and decreased the number of reinforcers obtained. The increase in response rates could be attributed to both a shift in the median inter-response time (IRT) to shorter intervals, and to a marked, dose dependent increase in the occurrence of bursts of responses (responses occurring within 3 s of a previous response). In contrast, NBQX and GYKI 52466 both decreased response rates in a dose dependent fashion, and did not shift the distribution of the IRTs, or increase the occurrence of burst responding. In the DMTP procedure, accuracy of matching decreased with increasing delay (up to 30 s, between presentation of sample and opportunity to respond). NBQX disrupted responding at a dose of 7.5 mg/kg, but lower doses were ineffective in influencing accuracy of performance of the discrimination. In contrast, MK 801 (0.1 and 0.2 mg/kg) reduced accuracy of matching at all delays, while tending to increase the speed of responding. These data demonstrate differences in the effects of AMPA and NMDA antagonists on performance of well trained operant behaviour.

Effects of benzodiazepine receptor ligands on the performance of an operant delayed matching to position task in rats: opposite effects of FG 7142 and lorazepam.

The effects of a series of benzodiazepine (BZ) receptor ligands, ranging from a full agonist through to partial inverse agonists, were examined on short term working memory in the rat. The behavioural paradigm used was a discrete trial, operant delayed matching to position task, as originally described by Dunnett (1985), with delays of 0, 5, 15 and 30 s. The benzodiazepine receptor (BZR) full agonist lorazepam (0.25, 0.375 and 0.5 mg/kg) dose and delay dependently impaired matching accuracy. Lorazepam also increased the latency to respond and decreased the number of nose pokes made into the food tray during the delays. In contrast, the BZR partial agonist ZK 95,962 (1, 3, 10 mg/kg) did not affect matching accuracy, but did increase the speed of responding. The BZR antagonist ZK 93,426 (1.25, 5, 25 mg/kg) had no effects in this paradigm. The BZR weak partial inverse agonists Ro 15-4513 (0.1, 1 and 10 mg/kg) and ZK 90,886 (1, 3 and 10 mg/kg) did not affect accuracy of performance. However, both of these drugs increased the latency to respond and decreased nose poke responses. These motoric effects were particularly strong following 10 mg/kg Ro 15-4513. This shows that the effects of drugs on the accuracy of responding and on the speed of responding can be dissociated. The BZR partial inverse agonist FG 7142 had effects on matching accuracy that were dependent upon dose. The lowest dose of FG 7142 (1 mg/kg) significantly improved accuracy, whereas the highest dose (10 mg/kg) impaired accuracy.(ABSTRACT TRUNCATED AT 250 WORDS)

Contrasting effects of the competitive NMDA antagonist CPP and the non-competitive NMDA antagonist MK 801 on performance of an operant delayed matching to position task in rats.

The effects of the competitive NMDA antagonist CPP and the non-competitive NMDA antagonist MK 801 (dizolcipine) on short term working memory in the rat were investigated. The behavioural paradigm used was discrete trial, operant delayed matching to position, as originally described by Dunnett (1985), with delays of 0, 5, 15 and 30 s. These delays generated an orderly "forgetting" curve in control rats, with matching accuracy decreasing from approximately 100% at 0-s delay to approximately 75% at 30-s delay. Intraperitoneal (IP) administration of CPP (10 mg/kg) produced a marked delay dependent impairment in performance, suggesting a specific effect on short term working memory. This effect was accompanied by a minor decrease in the speed of responding, and a slight increase in the number of missed trials. Lower doses of CPP had no significant effects on either matching accuracy or sedation. In contrast, IP administration of MK 801 (0.1 and 0.2 mg/kg) caused a marked delay independent impairment in the accuracy of delayed matching performance, suggesting a non-specific disruption of performance. A lower dose (0.05 mg/kg) of MK 801 had no significant effect on matching accuracy. The two lower doses of MK 801 increased the number of nose pokes made during the delays and tended to increase the speed of responding, suggesting a stimulant-like action. The highest dose of MK 801 had the opposite effects and also decreased the number of trials completed.(ABSTRACT TRUNCATED AT 250 WORDS)

5-HT1A receptor agonists improve the performance of normal and scopolamine-impaired rats in an operant delayed matching to position task.

A series of experiments examined the effects of 5-HT1A ligands alone and in combination with the muscarinic antagonist scopolamine on short term working memory in the rat. The behavioural paradigm was a discrete trial, operant delayed matching to position task, with delays of 0, 5, 15 and 30 s. The 5-HT1A ligands tested were the full agonist, 8-OH DPAT (0, 0.1, 0.3 and 1 mg/kg), the partial agonist, ipsapirone (0, 1, 3 and 10 mg/kg), and the purported antagonist, NAN 190 (0, 1, 2, and 4 mg/kg). 1-PP (0, 0.1, 0.3, 1 mg/kg), the major metabolite of ipsapirone, was also tested. The lowest dose of 8-OH DPAT significantly improved matching accuracy at the longest delay, whereas the highest dose impaired matching accuracy and increased the latency to respond. Ipsapirone also significantly improved the accuracy of performance at a dose of 3 mg/kg, but the doses of 1 and 10 mg/kg did not significantly affect performance. NAN-190, at the highest dose tested (4 mg/kg), impaired matching accuracy, whereas the two lower doses did not significantly affect performance. The highest dose also increased the latency to respond. 1-PP had no effect on performance. Scopolamine HBr (0.14 mg/kg) caused a delay dependent impairment in matching accuracy, and had no effect on missed trials or the latency to respond. Low doses of 8-OH DPAT (0.1 and 0.3 mg/kg) significantly attenuated the scopolamine induced accuracy impairment, whereas 1 mg/kg 8-OH DPAT potentiated the impairment. Ipsapirone (3 mg/kg) also significantly improved the performance of scopolamine impaired rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of several benzodiazepine receptor ligands in two models of anxiolytic activity in the mouse: an analysis based on fractional receptor occupancies.

This study compared the effects of the beta-carboline anxiolytic, abecarnil, with other benzodiazepine receptor (BZR) ligands, including the full agonists diazepam and alprazolam, and the partial agonists ZK 95962 and bretazenil (Ro 16-6028), and alpidem, in the mouse four-plate test and plus-maze. The efficacy and potency of each compound was related to the fraction of BZR occupied by the drug. Abecarnil was efficacious in both tests and showed anxiolytic effects comparable with alprazolam and diazepam. In the four-plate test, abecarnil, bretazenil, and ZK 95962 had selective effects on releasing exploratory locomotor activity suppressed by footshock (punished crossings). None of these compounds significantly altered non-punished crossings. In contrast, diazepam and alprazolam increased both unpunished and punished crossings at low to medium doses (receptor occupancies of approximately 20-60%). The number of punished and unpunished crossings fell to control levels or below at higher, more sedative doses (approximately 80% receptor occupancy). Alpidem had very weak anxiolytic-like effects in this test and markedly reduced unpunished crossings at relatively low receptor occupancies (> 15%). In the plus-maze, abecarnil increased the time spent in the open arms and the percentage open arm entries to an extent equal to that observed following diazepam or alprazolam administration. Bretazenil and ZK 95962 had weak effects on the measures of anxiolytic activity in this test. Alpidem also had little anxiolytic-like activity in the plus-maze but markedly reduced the total number of arm entries.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of benzodiazepine receptor partial inverse agonists in the elevated plus maze test of anxiety in the rat.

The present series of experiments examined the effects of five benzodiazepine receptor (BZR) partial inverse agonists on the behaviour of rats on an elevated plus maze. The drugs were tested in a standard plus maze with 3-cm walls added to the open arms, as this has been shown to increase the sensitivity of the plus maze to anxiogenic-like drugs effects (Jones and Cole 1995). The drugs tested were FG 7142 (0-100 mg/kg), beta-CCE (0-30 mg/kg), ZK 132,556 (0-100 mg/kg), ZK 90 886 (0-30 mg/kg) and Ro 15-4513 (0-30 mg/kg). In addition, to allow a comparison with previous studies, the effects of three reference substances, DMCM (0-2.5 mg/kg), pentylenetetrazol (PTZ; 0-30 mg/kg) and yohimbine (0-5 mg/kg), were also examined. These three reference compounds produced a dose-dependent reduction in the duration of open arm exploration and the total number of open arm entries, indicative of anxiogenic-like effects. DMCM produced significant effects at the doses of 1.25 and 2.5 mg/kg, PTZ at 30 mg/kg, and yohimbine at 5 mg/kg. The BZR partial inverse agonist FG 7142 (10, 30 and 100 mg/kg) also reduced the duration of open arm exploration and the total number of arm entries. The minimally effective dose resulted in a receptor occupancy of approximately 80%. Ro 15-4513 also produced anxiogenic-like effects, but only at a dose (30 mg/kg) that resulted in a receptor occupancy of approximately 95%.(ABSTRACT TRUNCATED AT 250 WORDS)

Endogenous corticotropin-releasing factor modulates feeding induced by neuropeptide Y or a tail-pinch stressor.

Previous work has characterized an anorexic action for endogenous, central nervous system corticotropin-releasing factor (CRF). Central injection of CRF decreases food intake induced pharmacologically by various appetite stimulants and a CRF antagonist attenuates restraint stress anorexia. Also, stressful physiological stimuli that are relevant to ingestive regulation, such as glucoprivation and protein nutrient deficiency, activate CRF systems. The present experiments examined the effects of exogenously administered CRF and a CRF antagonist, alpha-helical CRF(9-41), on spontaneous feeding induced by neuropeptide Y (NPY) and by a tail-pinch stressor. Pretreatment with a low dose of the CRF antagonist (1 microgram ICV) enhanced the hyperphagia induced by NPY while reducing the latency to begin feeding and increasing the duration of eating during tail pinch. Higher doses of alpha-hel CRF (5 and 25 micrograms ICV) exhibited diminishing or opposite effects. In contrast, CRF pretreatment (0.02, 0.1, and 0.5 microgram ICV) blocked the acquisition of tail-pinch feeding. Hence, while CRF administration impairs intake in these and other feeding paradigms, alpha-hel CRF actually facilitated dose dependently the intensity of the feeding response to NPY and tail pinch. These results suggest that endogenous CRF systems may play a role in modulating excessive feeding under conditions of evoked appetite and that brain CRF systems regulate feeding when excessive intake threatens to compromise the performance of other noningestive behaviors.

Effects of 6-hydroxydopamine lesions of the nucleus accumbens septi on performance of a 5-choice serial reaction time task in rats: implications for theories of selective attention and arousal.

Six experiments examined the effects of 6-hydroxydopamine (6-OHDA) induced lesions of the nucleus accumbens septi (NAS) on performance of a spatial discrimination. The behavioral paradigm used was an analogue of Leonard's 5-choice serial reaction time task for humans. The 6-OHDA lesion produced an 87% depletion of dopamine (DA) in the NAS, only a minor (25%) depletion of DA in the anterior caudate, and a 75% depletion of neocortical noradrenaline (NA). The lesion transiently attenuated both the speed and impulsivity of responding on the baseline schedule, but did not affect discriminative accuracy. In addition, the lesion attenuated the increase in premature responding caused by both systemic administration of D-amphetamine and bursts of loud white noise, presented just prior to the onset of the visual discriminanda. However, the lesion did not affect discriminative accuracy in these 2 conditions. The lesion also only had extremely minor effects on performance of this paradigm when the intertrial intervals were unpredictable. These results contrast with the previously reported pattern of behavioral effects resulting from forebrain NA depletion in the same behavioral paradigm. They therefore complete a double dissociation of effects on accuracy and vigour of responding, supporting theories of a division of arousal-type processes.

Damage to ceruleo-cortical noradrenergic projections impairs locally cued but enhances spatially cued water maze acquisition.

A series of 4 experiments tested the effects of central catecholamine depletion on acquisition of an escape response in a spatial water maze. In Expt. 1, local infusions of 6-hydroxydopamine (6-OHDA) into the dorsal noradrenergic bundle (DNAB) enhanced efficient acquisition of the spatial water maze in a stressful condition (cold water), but had no effect in warm water. In Expt. 2, lesions of the ventral noradrenergic bundle did not affect acquisition of the maze, indicating that the changes observed in Expt. 1 were unlikely to have been the result of incidental damage to the noradrenergic innervation of the hypothalamus. Measures of core body temperature and plasma corticosterone were taken in parallel with the behavioral experiments and revealed that central noradrenaline (NA) depletion did not alter these responses to cold or warm water swims. Expt. 3 revealed a contrasting pattern of effects following dopamine (DA) depletion from the caudate-putamen: swimming speed was reduced in warm, but not cold water and maze acquisition was impaired, to an equal extent in warm and cold water. Finally, in Expt. 4, rats with 6-OHDA lesions of the DNAB were impaired in discriminating local cues in a simultaneous visual discrimination water maze. These results support the hypothesis that ceruleo-cortical NA depletion broadens the span of attention, particularly under stressful circumstances. In contrast, the results also indicate that striatal DA depletion mainly affects vigour of responding, as measured by swim speed, and that this effect can be reversed by the stressful effects of cold water.

Lesions of the dorsal noradrenergic bundle simultaneously enhance and reduce responsivity to novelty in a food preference test.

In conclusion, DNAB lesions have been shown to have two, apparently contradictory effects in a food preference test: to increase neophobia to a novel environment, and to increase the tendency to eat novel food in a novel environment. It has been suggested that these two effects occur because, although NA has a common action on neuronal firing in terminal fields, the dissociable consequences reflect the different functions of areas in receipt of these noradrenergic afferents. In addition, it has been shown that DNAB lesions, VNAB lesions, and a benzodiazepine, chlordiazepoxide, all have somewhat different behavioral effects in the food preference test. Taken together with the lack of correlation between the various behavioral measures used in these experiments, this suggests that neophobia does not reflect a single behavioral process, such as anxiety, or reactivity to novelty.

Central administration of corticotropin releasing factor induces long-term sensitization to D-amphetamine.

Corticotropin releasing factor (CRF) has been shown to initiate neuroendocrine and behavioral responses to stress. As stress and amphetamine (AMPH) show cross-sensitization, we investigated the role of endogenous CRF in behavioral sensitization to D-AMPH. In order to evaluate the participation of the central action and the pituitary-adrenocortical (PA) stimulatory effect of CRF, we compared the effects of repeated intracerebroventricular (i.c.v.) administration of CRF (0, 0.5, 2.5 micrograms/2 microliters), which have central and neuroendocrine consequences, with those of repeated subcutaneous administration of CRF (0, 0.1, 0.5, 2.5 micrograms/250 microliters), doses which only stimulate the PA axis, on the development of sensitization to AMPH-induced motor activation administered 1 week later. Repeated i.c.v. administration of CRF induced a long-lasting enhancement of the hyperactivity induced by 0.75 mg/kg peripheral administration of D-AMPH, whereas no sensitization to D-AMPH was observed following repeated subcutaneous administration of CRF. These results favor the hypothesis that a centrally mediated action of CRF is involved in the cross-sensitization of psychostimulants and stress.