摘要:

Animals neonatally depleted of dopamine show decreases in exploratory behaviour. As latent learning may depend on exploratory behaviour the present study was undertaken to examine the effects of neonatal dopamine depletion on latent learning. In two experiments dopamine was depleted neonatally, using 6-hydroxydopamine injected intracisternally on day I after birth. In both experiments, exploratory behaviour, measured as rearing and head-dip responses in a modified openfield/holeboard, was reduced in the dopamine depleted rats whereas ambulatory behaviour was elevated. In a modified radial arm maze also, rearing responses were decreased while ambulation was increased for the 6-hydroxydopamine treated rats. Latent learning was tested in each experiment following preexposure to the maze for either a single trial or four trials. 6-Hydroxydopamine treated rats demonstrated a comparable latent learning effect to vehicle treated rats after four maze exposures but showed a greatly attenuated latent learning effect following only a single exposure. It is suggested that the effects of neonatal dopamine upon maze and latent learning are secondary to the effects on hyperactivity, reduced exploration and/or increased neophobia shown by these rats.

ISSN:0955-8810    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The present study examined the effects of acute and chronic treatment with the alpha-2-adrenoceptor agonist clonidine on behavior in the Conditioned Suppression of Drinking (CSD) conflict paradigm, an animal model for the study of anti-anxiety treatments. In daily 10-min sessions, water-deprived rats were trained to drink from a tube which was occasionally electrified (0.25 mA). Electrification was signalled by a tone. Within 3–4 weeks of 4 day/week CSD sessions, control (i.e. non-drug) CSD behavior had stabilized (approximately 40 shocks/session and 11 ml water/session). Acute treatment with clonidine across a range of doses (1.25–40 $mUg/kg; 10-min pretreatment) did not exert an anti-conflict effect, with doses greater than 5 $mUg/kg significantly depressing unpunished responding (i.e. water intake). Similarly, administration of a single dose of clonidine (40 $mUg/kg) across a range of pretreatment times (10 to 120 min) failed to increase punished responding. In contrast, chronic post-test treatment with clonidine (40 $mUg/kg, twice daily for 18 weeks) resulted in a dramatic and time-dependent increase in punished responding, with a latency to onset of approximately 3–4 weeks. The response to an acute challenge with chlordiazepoxide (10 mg/kg) or the benzodiazepine antagonist Ro 15–1788 (4.0 mg/kg) did not differ in chronic clonidine-versus saline-treated subjects, indicating that benzodiazepine receptor sensitivity had not been affected by this chronic clonidine treatment. An acute challenge with a low dose of clonidine (10/$mUg/kg) decreased punished and unpunished responding in chronic clonidine- or saline-treated subjects. Finally, an acute challenge with the alpha-2-antagonist yohimbine (1.25 mg/kg) failed to block the increase in punished responding associated with chronic clonidine treatment, indicating that the anti-conflict effect of this chronic post-test clonidine treatment was not the result of alpha-2-adrenoceptor activation at the time of CSD testing (i.e. not due to drug accumulation). Discontinuation of chronic clonidine treatment resulted in a decline to near saline-treated levels of punished responding over the course of 3 weeks of conflict testing. The relationship of these findings to the anti-anxiety effects of clonidine in humans are discussed.

ISSN:0955-8810    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The repeated injection of drugs which increase locomotion, paired with a distinctive testing environment, has been shown to result in conditioned hyperactivity upon subsequent exposure to the environment alone. Unknown, however, are the form and characteristics of the behavioral response that makes up the conditioned hyperactivity. Conditioned and unconditioned locomotor responses in rats were compared with a computerized Behavioral Pattern Monitor (BPM), a system which provides detailed information regarding the amount and qualitative patterning of locomotor activity and investigatory responses. After an initial 2 h exposure to the BPM chambers (baseline day), rats were randomly assigned into one of two groups and injected each day with saline or 0.75 mg/kg amphetamine (AMPH) prior to placement in the BPM chambers for a 2h experimental session. Rats were then returned to their home cages and injected with the alternate solution. This procedure was repeated for 5 days, and on the sixth day all rats were injected with saline prior to placement in the BPM. Rats that had received AMPH/BPM pairings exhibited significant increases in horizontal locomotion, rearing and investigatory holepokes on the test day compared to rats that received saline/BPM pairings. The AMPH group also exhibited an increased sensitivity to a physical movement of the test chambers. Analyses of the daily locomotor paths for each rat using transition matrices revealed that the conditioned activity measured on the test day resembled the last AMPH day more than either the first AMPH day or the predrug baseline day. These descriptive measures of each animal's spatial patterns of locomotion suggest that the particular pattern induced by AMPH in each animal stabilized over time and became conditioned to environmental cues. In this case, the increased motor activity observed on the test day was qualitatively similar to the unconditioned response produced by AMPH.

ISSN:0955-8810    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The generation of adjunctive behavior was studied in rhesus monkeys responding under fixed-interval (FI) schedules of food pellet delivery or intravenous (iv) infusions of cocaine or midazolam. The FI schedule value ranged from 1.5 to 120 min. Each response on a second, concurrently available lever resulted in an infusion of saline. The number of saline infusions received was a bitonic function (inverted U) of the interval of reinforcer (food or drug) delivery. This bitonic function is characteristic of adjunctive behavior and strongly suggests that the responding that results in the infusion of saline was an adjunctive behavior. Furthermore, these results establish that intermittent schedules of drug delivery can generate adjunctive behavior. Increases in the dose of drug self-administered shifted the bitonic function of saline infusions to the right. This shift in the function of adjunctive behavior is consistent with the hypothesis that the generation of adjunctive behavior is dependent upon both the magnitude and the intermittent delivery of the reinforcer.

ISSN:0955-8810    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

In a previous study it was found that the anxiolytic drug buspirone and the related compounds gepirone and ipsapirone disrupted the performance of a passive avoidance response by rats. A similar effect was not produced by several other drugs including chlordiazepoxide, imipramine and haloperidol. In the present study the same procedure was used to investigate whether other compounds known to interact with serotonergic mechanisms would produce a similar effect. The 5HT1Aagonists 8-OH-DPAT and MDL-72832 produced similar disruptions in the performance of a step-down passive avoidance response (i.e. decreased latencies), with 8-OH-DPAT giving rise to a bell-shaped dose-response curve. Neither ritanserin, a 5HT2antagonist, nor 1-PP, a metabolite of buspirone known to have α2-adrenoceptor antagonist properties, was active. Odansetron (GR38032F), a 5HT3antagonist, was active, although the magnitude of the effect was smaller than that seen with the 5HT1Aagonists and was not clearly dose-related. In drug interaction experiments the effect of 8-OH-DPAT was completely eliminated after treatment with NAN-190 although NAN-190 itself increased step-down latencies. The effect of 8-OH-DPAT was also partially blocked by prazosin. Thus the performance of a step-down passive avoidance response is disrupted by a range of compounds known to be 5HT1Aagonists but by few other drugs.

ISSN:0955-8810    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Peripherally administering the serotonin (5-HT) analogs, α-methyl-5-hydroxytryptamine (α-Me-5-HT) and 5-carboxamidotryptamine (5-CT), reduced milk consumption by food-deprived rats. 5-CT decreased milk intake 100-fold more potently than α-Me-5-HT (ID50's = .06 and 5.6$mUmol/kg, respectively). 5-CT also elicited drinking but α-Me-5-HT did not. The nonselective 5-HT antagonist, methysergide, blocked the anorectic actions of each agonist. By contrast, the 5-HT2antagonist, ketanserin, and the peripheral 5-HT22antagonist, xylamidine, only prevented anorexia due to α-Me-5-HT. These results suggest that stimulating either peripheral 5-HT2or peripheral 5-HT1-like receptors inhibits feeding in rats. 5-HT1-like sites may also mediate 5-HT-induced drinking.

ISSN:0955-8810    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Lever-press responding of male Sprague-Dawley rats was maintained under a conflict procedure in which every tenth response produced both food and electric shock (punished responding); every thirtieth response produced only food in the presence of a separate stimulus. The benzodiazepines, diazepam and chlordiazepoxide, increased responding 4− to 6-fold. Buspirone and its structural analog, gepirone, only moderately and inconsistently increased responding (1.5− and 2-fold, respectively). The dopamine-2 (D-2) receptor antagonist, sulpiride, but not haloperidol had effects similar to buspirone. The D-l antagonist SCH 23390 was not active. The non-selective serotonin (5HT) antagonists, cyproheptadine and methysergide, consistently increased responding 2-fold, but the 5HT-2 antagonists, ketanserin, pirenperone, ritanserin, R-56 413, and LY 53857 and the 5HT-1A agonist, 8-OH-DPAT, were inactive. In pigeons, serotonergic compounds have been shown to increase punished responding. The present results suggest that exploitation of this species difference may be helpful in evaluating new chemicals for novel anxiolytic activity and for investigation of their mechanisms of action.

ISSN:0955-8810    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The effects of a prefrontal dopamine (DA) lesion were compared to those induced by a combined DA and noradrenaline (NA) lesion, to investigate the permissive role of prefrontal NA terminals in the anxiolytic-like effect of a prefrontal DA lesion. Lesions consisted of bilateral microinjections of 6-hydroxydopamine into the medial prefrontal cortex in rats either given desipramine (25 mg/kg) before surgery (DA lesion) or not pretreated with desipramine (combined DA and NA lesions). Three weeks post-surgery, water-restricted rats, given saline or diazepam (2 mg/kg), were subjected to a single session in the punished drinking test. Prefrontal DA lesions significantly increased punished drinking in saline-treated rats. This effect was not observed in rats with the dual prefrontal lesions. The ability of diazepam to increase punished drinking was not modified by either lesion. These data suggest that the integrity of NA afferents to the prefrontal cortex is necessary for the anxiolytic-like effect induced by the prefrontal DA lesion. The results also indicate that the effect of diazepam is not mediated by the prefrontal catecholamine afferents.

ISSN:0955-8810    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Pigeons (n= 4) were trained to discriminate cocaine (3.0 nig/kg, i.m.) from saline in a two-key, food-reinforced drug discrimination paradigm. After acquisition of the discrimination, the H1-antihistamines, chlorpheniramine, tripelennamine, diphenhydramine, promethazine and hydroxyzine, were administered before test sessions to determine if these antihistamines shared discriminative stimulus (DS) effects with cocaine. Chlorpheniramine (0.3–5.6 mg/kg) and tripelennamine (0.1–1.7 mg/kg) substituted, (i.e. > 80% cocaine-key responding) in all four birds. Diphenhydramine (0.1–10 mg/kg) and promethazine (0.1–56 mg/kg) substituted for cocaine in three and two birds, respectively, while hydroxyzine (1.0–100 mg/kg) did not substitute for the training drug in any bird. These results, in conjunction with results from a previous study in which several antihistamines shared DS effects withd-amphetamine, suggest that the DS effects of some H1-antihistamines may be similar to those of psychomotor stimulants.

ISSN:0955-8810    

出版商:OVID    

年代:1990

数据来源: OVID