Effects of dopamine D1 and D2 receptor antagonists on cocaine-induced place preference conditioning in preweanling rats

The effects of dopamine D1 and D2 receptor antagonists on the reward processes of 10- and 17-day-old rats were assessed using the conditioned place preference paradigm. Conditioning and testing were conducted in a three-compartment chamber, with each end compartment having its own distinct tactile and odor cues (almond and lemon). During six experiments, 10- and 17-day-old rats (age at initial conditioning) were injected intraperitoneally with either saline, the dopamine D1 receptor antagonist R(+/-)-SCH 23390 hydrochloride (0.01-1.0 mg/kg), or the dopamine D2 receptor antagonists (+/-)-sulpiride (1-100 mg/kg) or S(-)-eticlopride hydrochloride (0.1-0.5 mg/kg) 30 min prior to being injected with cocaine hydrochloride (20 mg/kg) or saline. After the latter injections, rats were immediately confined in the lemon-scented (nonpreferred) compartment for 30 min. On the alternate conditioning day, rats were injected with saline and confined in the almond-scented compartment. On the third day (i.e., the test day), rats were given saline and allowed free access to the entire chamber for 15 min. The results showed that the dopamine D1 receptor antagonist SCH 23390 blocked the cocaine-induced place preference conditioning of both 10- and 17-day-old rats. Surprisingly, the dopamine D2 receptor antagonists sulpiride and eticlopride blocked the place preference conditioning of 10-day-old rats, while leaving the 17-day-old rats unaffected. These results indicate that dopamine D1 receptors are critically involved in the reward processes of preweanling rats, but that the importance of dopamine D2 receptors changes across ontogeny.     

CDK4, a possible critical regulator of apoptosis in rat pheochromocytoma PC12 cells

Rats infused subcutaneously with 9 mg/kg/day nicotine tartrate for 7 days exhibit behavioral abstinence signs following either termination of nicotine infusion or injection of the noncompetitive nicotinic antagonists mecamylamine (s.c.) or hexamethonium (ic.c.v.). This study examined the abstinence precipitating effects of dihydro-beta-erythroidine (DHbetaE), a competitive nicotinic antagonist. Twenty-four nicotine-dependent rats were injected in the third ventricle with 10, 18, or 25 microg DHbetaE in 20 microl saline or with saline alone and observed for abstinence signs over a 20-min period. There was a significant positive linear trend of overall abstinence signs as a function of dose, p < 0.01. In 12 nondependent rats, the high dose of DHbetaE did not induce more abstinence-like signs than saline alone. In a second experiment, 18 nicotine-dependent rats were injected s.c. with 1 or 6 mg/kg of the muscarinic antagonist scopolamine or with saline alone. Few abstinence signs were observed in any group: there was no significant drug effect. The results suggest that nicotine abstinence signs observed in the rat are specific to reduced stimulation of previously overstimulated nicotinic receptors.     

Pavlovian inhibitory conditioning and tolerance to pentobarbital-induced hypothermia in rats.

One group of rats (discrimination group) from an S pool of 96 male Sprague-Dawley rats received training in which, on alternate days, 1 conditioned stimulus (CS+) was associated with administration of 30 mg/kg pentobarbital (PBB), and a different CS (CS–) with saline. Controls received either exposure to both CSs but not the drug or to the drug but no CSs or to neither the CSs nor the drug. Subsequently, half the Ss in each group received injections of PBB in the presence of one of the CSs and the remaining half in the presence of the other CS. Results show that the discrimination group injected with PBB in the presence of CS+ displayed the most tolerance, whereas the discrimination group injected with PBB in the presence of CS– displayed the least tolerance. The attenuation of tolerance in the discrimination group injected in the presence of CS– provides evidence of inhibitory Pavlovian conditioning. Additional evidence of inhibitory conditioning was provided by the fact that CS? enhanced the hypothermic effects of PBB in the discrimination group, whereas CS? attenuated these effects. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Scopolamine's effect on passive avoidance behavior in immature rats

Male albion rats ranging in age from 15-30 days were injected with either scopolamine hydorbromide or saline, prior to training and retention testing on a black-white passive avoidance (PA) task. Pretraining administration of a 1.0-mg/kg dose of scopolamine significantly increased the median number of trails to criterion for 18-, 21-, and 30-day-old rat pups when compared with their saline controls. Fifteen-day-olds showed drug-related PA deficits when a 2.0-mg/kg dose was given. Retention data reflect characteristic age-dependent memory loss over the 1-week acquistionretention period with no apparent state-dependent effects. The data suggest the presence of cholinergic inhibitory mediation of PA responding in preweanling and postweanling pups.     

Conditioning of food aversions by injections of psychoactive drugs.

Injected male Sprague-Dawley rats with various drugs or saline immediately after drinking milk for the 1st time. 1 wk. later Ss were again given access to the milk. Conditioned aversion to the milk was produced by moderate doses of scopolamine, scopolamine methyl nitrate, amphetamine, lorazepam, and chlorpromazine. Conditioned aversion was not obtained if scopolamine was injected 30 min. prior to milk drinking or more than 4 hr. afterward. (22 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Doxorubicin, vincristine, and cis-diamminedichloroplatinum (II) therapy in patients with advanced breast cancer

Thirty-six male albino rats were injected with either saline or 0.6 mg/kg scopolamine and placed on a metal grid. The grid was wired to a transistor-biased detector which determined, every second, whether the subject's resistance was above or below a preset threshold value. Over test sessions of five minutes, drug subject's resistances were above each of the three threshold values used (5, 10, 15 megohms) for significantly longer than those of control subjects. Scopolamine treated rats would therefore receive lower shock levels than control subjects in a shock experiment.     

Ontogeny of morphine withdrawal in the rat.

The present studies examined behavioral changes during precipitated morphine withdrawal in 7- to 42-day-old rat pups. One group of rats was injected with morphine sulfate (10.0 mg/kg) twice daily for 6.5 days. Another group of 7-day-old rats received a lower dose of morphine (3.0 mg/kg). Controls were saline injected or untreated litters (7-day-old pups only). On Day 7, a target pup was injected with saline or naltrexone (0.3–20.0 mg/kg). Preweaning pups were observed in a warm chamber with the litter. Forty-two-day-old rats were tested individually. Morphine-treated pups tested with naltrexone showed significant alterations in behavior that varied at different ages. For example, rolling, stretching, and head and paw moves were observed at the younger ages, whereas burrowing, diarrhea, jumps, teeth chatter, and wet dog shakes occurred in the older rats. These data indicate that morphine-abstinent rats demonstrate withdrawal signs that are within the developmental repertoire of the rat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Etiological role of cadmium in hypertension in an animal model

Dahl hypertension-resistant (R) and hypertension-sensitive (S) lines of rats were used to determine whether cadmium plays an etiological role in hypertension. In Study I, weanling (3-week-old) R and S rats of both sexes were given a low-salt (0.4% NaCl) diet and were divided into two groups. Rats in the cadmium group were injected with cadmium (2 mg/kg body weight, ip), whereas the controls received identical volumes of saline. Three weeks after the first injection, no elevations of systolic blood pressure were detected. A second dose of cadmium (1 mg/kg) produced hypertension in S females but not in S males or in R rats of either sex. Also, female S cadmium rats manifested significant (p less than 0.01) mild to moderate renal vascular changes. The concentrations of cadmium in hepatic and renal tissues of S cadmium rats were significantly higher (p less than 0.001) than in R rats. In Study II, weanling (3-week-old) female S rats on a high-salt (4% NaCl) diet were given cadmium (2 mg/kg body weight, ip) at week 3 followed by second and third injections of cadmium (1 mg/kg) at weeks 6 and 23. S controls received the same volumes of saline. Cadmium enhanced the rate and the degree of salt-induced hypertension development. Pathological lesions of periarteritis nodosa in the mesenteric arteries and renal vascular lesions occurred to the same extent in the cadmium and control groups. These data indicate that differences in genetic background influence the development of cadmium-induced hypertension in weanling rats, and that cadmium exacerbates the severity of salt-induced hypertension.     

Cholinergic influences in habituation of exploratory activity in mice.

Injected 30 male mice, chosen from a random-bred strain (ICR), with either saline, scopolamine, or methscopolamine. Ss were then allowed to explore a chamber, and locomotor activity was monitored every 7.5 min by photocells. Ss treated with saline and methscopolamine displayed a significant decrement in activity over the course of an exposure session, but Ss injected with scopolamine did not show this decrement. The decline in activity over time was considered to reflect habituation of exploratory responses in a novel environment. Results are interpreted in terms of the disruptive effects of scopolamine on habituation. It is concluded that activity of brain acetylcholine is critical to the process of habituation of locomotor activity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lithium chloride and avoidance of novel places.

In Exp I, 40 male hooded rats were exposed to a distinctive chamber (Chamber A, part of a 2-chamber apparatus) that was novel for half of the Ss but familiar for the other half. Each S was subsequently injected with lithium chloride or saline. In a test trial conducted 24 hrs later, all Ss were given a choice between Chamber A and Chamber B, which was novel for all Ss. The group made familiar with Chamber A and then given lithium showed a significant preference for that side or an avoidance of the novel side, a "spatial neophobia." Exp II, with 40 Ss, confirmed the spatial neophobia effect and demonstrated that it did not depend on the particular conditioning procedure used in the 1st experiment. The spatial neophobia effect was related to similar effects in the taste aversion literature and to the results of research on lithium-induced decreases in exploratory behavior. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The muscarinic acetylcholine antagonist scopolamine impairs short-distance homing pigeon navigation

The present study employed intramuscular (i.m.) injections of the acetylcholine (ACh) receptor antagonist scopolamine hydrobromide (0.10 mg/kg) to investigate the possible involvement of ACh in naturally occurring spatial navigation in homing pigeons (Columba livia). Control pigeons receiving injections of saline or scopolamine methylbromide, an ACh antagonist that does not cross the blood-brain barrier, were oriented in a homeward direction when released from a location 8 km from home. In contrast, pigeons injected with scopolamine hydrobromide (0.10 mg/kg, i.m.) were less well oriented and took more time to return home from the same location. These results suggest that homing pigeon navigation is regulated, in part, by central cholinergic mechanisms.     

Interactions between D1 and muscarinic receptors in the induction of striatal c-fos in rats depleted of dopamine as neonates

The contributions of striatal D1 receptors to the expression of sensorimotor behavior are qualitatively different in rats depleted of dopamine (DA) as neonates vs. as adults. In an effort to reveal neuronal mechanisms underlying these behavioral difference we determined the effects of the partial D1 agonist SKF 38393, the muscarinic antagonist scopolamine, and the combination of the two drugs on the induction of c-fos in the striatum and its projection sites, the globus pallidus and substantia nigra. Adult rats, given intracerebroventricular injections of 6-hydroxydopamine (6-OHDA, 50 micrograms/5 microliters/hemisphere) or its vehicle on postnatal day 3, were treated with SKF 38393 (1.5 mg/kg, i.p.), scopolamine (5.0 mg/kg, i.p.) or the combination of the two drugs. There was no significant induction of c-fos in vehicle-treated controls, regardless of drug administration. In DA-depleted rats, scopolamine also did not induce c-fos whereas SKF 38393 produced a significant increases in the number of FOS-positive cells in the dorsal, but not ventral, striatum. The combined administration of scopolamine and SKF 38393 resulted in a potent synergism in the number of FOS-positive cells in DA-depleted rats. These interactions between lesion condition and drugs on c-fos induction were not secondary to differences in drug-induced behavioral activity. Activity levels were no different in vehicle vs. DA-depleted rats following the combined administration of scopolamine + SKF 38393, yet the two groups of rats exhibited marked differences in the density of FOS-positive striatal neurons. The effects of scopolamine and SKF 38393 on c-fos induction in striatum are qualitatively similar to those reported in rats DA-depleted as adults and suggest that, at this single-label level of analysis, the ability of D1 and muscarinic receptors to influence striatal activity does not contribute to the marked age-related differences in the behavioral effects of DA depletions.     

The septohippocampal cholinergic system and classical conditioning of the rabbit's nictitating membrane response.

28 New Zealand albino rabbits received bilateral microinjections of scopolamine (1 μl) or saline into either the dorsal hippocampus (Exp I) or the medial septal nucleus (Exp II). Ss then underwent classical conditioning of the nictitating membrane response in which a light served as a CS and eye shock served as the UCS. Results indicate that whereas hippocampal injections of scopolamine had no effect on conditioning, scopolamine injected into the medial septum retarded acquisition of the response. A 3rd experiment indicated that this retardation of conditioning was not due to changes in sensitivity to either the CS or UCS. Results are discussed in terms of accumulating evidence that manipulations that produce certain patterns of activity in the hippocampus are detrimental to acquisition of the nictitating CR. (43 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparative effects of scopolamine and amphetamine upon behavioral reactivity and visual evoked potentials to flashes in rats.

Two experiments employed a total of 14 male Holtzman rats in which averaged visual evoked response (VER) at cortex and behavioral reactivity to photic stimuli were examined following administration of varying dosages of either scopolamine (and methyl scopolamine) or dextroamphetamine, and of saline. The augmentation in behavioral activity produced by scopolamine and dextroamphetamine was associated with differential patterns of changes in VERs. Scopolamine reduced the amplitude of the early negative component, enhanced the early positive component, and blocked the attenuation of the late negative wave normally associated with heightened behavioral activity. Amphetamine produced relatively selective decrements in the late negative wave, which at higher dosages related to flash sequence. This information is of interest in utilizing VERs to help distinguish different antecedents of "behavioral arousal" to photic stimulation. (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Scopolamine affects response-to-change test involving 20-min retention interval after locomotor exploration in rats

The tendency to select the T-maze arm that has been changed in brightness between two successive trials (response-to-change) was investigated. Our previous findings indicated that scopolamine injections (1.0 mg/kg) impaired responding to change of brightness in a choice trial (trial II) following a 1-min retention interval, when in the first acquisition trial rats could only inspect the white-black T-maze arms through transparent partitions (the passive test). The drug was ineffective when rats were allowed locomotor exploration of the maze (the active test). The aim of the present experiment was to investigate the effect of the same dose of scopolamine on the active test involving a longer 20-min retention interval between the acquisition trial and the choice trial. The effect of cue salience also was examined by using grey-black arms. Rats injected with scopolamine (Scopo) 20 min before the acquisition trial performed in the white-black maze on the chance level, whereas saline-injected rats (Sal) showed significant preference for the changed arm. Decreasing the cue salience impaired response-to-change in Sal rats (50% of changed arm choices) but had no further effect on performance of Scopo rats, presumably because of a floor effect. The postacquisition injection had a somewhat stronger effect than the injections preceding acquisition, which most probably reflects the state dependency phenomenon. The deficient performance due to scopolamine treatment that appeared in the present study at a longer retention interval could be interpreted in terms of increased forgetting.     

Effects of scopolamine on spatial double alternation in rats.

Developed and tested a method for training spatial double alternation in 3 experiments, with a total of 4 male albino Wistar rats and 10 male albino Sprague-Dawley rats. Responding on different components of the sequence was controlled by different interoceptive and exteroceptive stimuli. This base line was used to compare the effects of scopolamine (.25-1 mg/kg) on the 2 sorts of cued responding in the same S. The 2 types of response did not differ appreciably in susceptibility to disruption by scopolamine. An analysis of errors showed that both switching and perseverative errors were increased by scopolamine, and that no lever preferences developed. An analysis of the various response sequences shows that in the same S, the probability of some sequences decreased consistently with increasing dose level, some sequences increased, and others showed an inverted -shaped function. (20 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral effects of GM1 ganglioside treatment and intrahippocampal septal grafts in rats with fimbria-fornix lesions

The monosialoganglioside GM1 is a compound with neurotrophic properties found to foster functional recovery in various paradigms of brain damage. The present experiment examined whether systemic treatment with GM1 may facilitate behavioral recovery in rats with fimbria-fornix lesions and intrahippocampal grafts rich in cholinergic neurons. Among 68 Long-Evans female rats, 46 sustained a bilateral electrolytic lesion of the fimbria and the dorsal fornix and 22 were sham-operated. Fourteen days later, half the lesioned rats were subjected to intrahippocampal grafts of a fetal septal cell suspension. Starting a few hours after lesion surgery and over a 2-month period, half the rats of each surgical treatment group received a daily injection of GM1 (30 mg/kg i.p.), the other half being injected with saline as a control. All rats were subsequently tested for locomotor activity and radial maze learning. The lesions induced locomotor hyperactivity and impaired learning performances in both an uninterrupted and an interrupted radial maze testing procedure. In all rats with surviving grafts, the grafts had provided the hippocampus with a new and dense organotypic acetylcholinesterase-positive innervation pattern which did not differ between saline- and GM1-treated subjects. The scores/performances of the rats that had received only the grafts or only the GM1 treatment did not differ significantly from those of their respective lesion-only counterparts. However, in the radial-arm maze task, the grafted rats given GM1 showed improved learning performances as compared with their saline-treated counterparts: they used more efficient visit patterns under the uninterrupted testing conditions and made fewer errors under the interrupted ones. The results suggest that GM1 treatment or intrahippocampal grafts used separately do not attenuate the lesion-induced behavioral deficits measured in this experiment. However, when GM1 treatment and grafts are used conjointly, both may interact in a manner allowing part of these deficits to be attenuated.     

Intrahepatic gas formation without abscess after hepatic artery thrombosis in the setting of liver transplantation

This paper reports that lesions of the medial frontal cortex (MFC) caused behavioral deficit in rats and that this deficit could be attenuated by a well formulated treatment with Org2766, an analog of ACTH-(4-9). Wistar rats were distributed in 3 groups: MFC lesion treated with saline (M-N); MFC lesion treated with Org2766 (M-O); and sham-operation treated with saline (S). Repeated Org2766 or saline injection commenced from the day of surgery and lasted for 13 days. After surgery, the rats were trained in a passive avoidance task and then in an active avoidance task. MFC lesions were found to be strongly associated with behavioral deficits. The M-N group rats displayed poor retention of the passive avoidance response and showed much slower learning of the active avoidance task as compared to S group rats. The result showed that chronic Org2766 administration improved the behavioral performance of both tasks in MFC lesioned rats. The also revealed that the superoxide dismutase (SOD) activity was significantly increased in the M-O group as compared to the M-N group 15 days after surgery. The possible mechanisms related to the beneficial effect of Org2766 on cortex damage are discussed.     

Posttraining intra-basolateral amygdala scopolamine impairs food- and amphetamine-induced conditioned place preferences.

The present study investigated the role of cholinergic muscarinic receptor function within the basolateral amygdala memory in the consolidation of conditioned place preference (CPP) memory. Adult male Long-Evans rats were confined to treatment- or nontreatment-paired compartments for 30 min on 4 alternating days. After training, rats received intrabasolateral amygdala infusions of scopolamine (2.5 μg or 5.0 μg/0.5 μl) or saline. The rats were then given a 20-min test session, and the time spent in each of the compartments was recorded. Immediate posttraining (but not delayed 2 hr) scopolamine (5.0 μg) blocked acquisition of food- and amphetamine-induced CPPs. The findings indicate a time-dependent role for basolateral amygdala muscarinic receptors in memory consolidation underlying CPPs for natural and drug rewards. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Maternal behavior in male rats: critical times for the suppressive action of androgens

The immediate and carry-over effects of scopolamine and d-amphetamine were evaluated in a free running Y-maze spontaneous alternation task. The immediate effect of scopolamine (1.0 mg/kg) or d-amphetamine (5.0 mg/kg) was to reduce alternation to chance or to levels significantly below chance (perseveration), respectively. On a second, non-drug test day alteration decreased in saline treated animals, but increased among mice which received scopolamine on Day 1. In contrast, upon retesting in the non-drug state, the performance of animals initially treated with d-amphetamine resembled that of saline treated mice. Subsequent experiments revealed that these effects could not be attributed to drug effects on peripheral mechanisms, consolidation, residual drug action or drug dissociated learning. It was concluded that the behavioral effects of scopolamine and d-amphetamine are qualitatively different. Whereas scopolamine disrupts habituation, d-amphetamine induces perseveration independently of any effects on habituation.