PubMed Health⌕ Search

Biomedical subjects

V Giardini

Publications and source records attributed to V Giardini.

16 recordsLinked to original sources
PubMed1990

Effects of dopamine depletion from the caudate-putamen and nucleus accumbens septi on the acquisition and performance of a conditional discrimination task.

Three experiments compared the effects of dopamine depletion from the caudate-putamen (CAUD; dorsal striatum) or nucleus accumbens septi (NAS; ventral striatum), or a systemically administered dopamine receptor antagonist (alpha-flupenthixol) on the acquisition and performance of a conditional discrimination task involving temporal frequency. In Expt. 1, rats receiving 6-hydroxydopamine (6-OHDA) lesions of the CAUD were impaired in the acquisition of a visual version of the task, and rats with 6-OHDA lesions of the NAS were not reliably impaired. Even when the rats with CAUD lesions had acquired the discrimination, they were still significantly slower to collect earned food pellets. Both CAUD and NAS lesions reduced a bias to respond to the faster of the two discriminative stimuli. In Expt. 2, rats with 6-OHDA lesions of CAUD were markedly impaired in their accuracy and speed of responding when they had been trained to criterion preoperatively. These effects could not be mimicked in controls by prefeeding (which had only minor effects on performance). Rats with 6-OHDA-induced lesions of the NAS were unimpaired in either visual or auditory discrimination performance, but were slower to extinguish responding than controls. In Expt. 3, alpha-flupenthixol (0.1-0.56 mg/kg, i.p.) produced dose-dependent impairments in both latency to respond and choice accuracy in visual and auditory versions of the task. In conjunction with other results, these data suggest that (1) dopamine receptor blockade and central dopamine depletion can impair discrimination performance under certain conditions (2) dopamine depletion from the ventral and dorsal striatum, respectively, have dissociable effects on behaviour controlled by conditioned reinforcers and discriminative stimuli and (3) the disruption of discrimination performance by dorsal striatal dopamine depletion is probably attributable to several factors.

Animals↗
PubMed1989

Effects of excitotoxic lesions of the substantia innominata, ventral and dorsal globus pallidus on visual discrimination acquisition, performance and reversal in the rat.

Rats received infusions of ibotenic acid into the substantia innominata, in the region of the nucleus basalis of Meynert (nbM), before and after training on simple (simultaneous) and conditional visual discriminations. The ibotenate infusions reduced cortical choline acetyltransferase (ChAT) levels by about 20%, destroyed many ChAT-immunoreactive neurons in the nbM, but also caused the loss of many neurons in the substantia innominata and adjacent areas. These lesions did not impair the acquisition and performance of a simple visual discrimination, but did impair reversal of the discrimination and the performance of a conditional visual discrimination. However, the degree of impairment was unrelated to the degree of cortical ChAT loss. Ibotenic acid lesions to the dorsal globus pallidus also impaired reversal of discrimination but left acquisition and performance unaffected. Striatal dopamine depletion produced by 6-hydroxydopamine (6-OHDA) infusions into the mid-ventral caudate nucleus impaired performance of the simultaneous visual discrimination. Cortical noradrenaline depletion produced by 6-OHDA lesions of the dorsal noradrenergic bundle either alone or in combination with ibotenic acid lesions of the substantia innominata had no effect on acquisition of the discrimination. It is concluded that ibotenic acid lesions of the substantia innominata or to the dorsal globus pallidus affect learning and performance of conditional visual discrimination performance and impair reversal learning without affecting the capacity to discriminate visual events. These results are compared to those following cortical noradrenaline depletion or striatal dopamine loss.

Animals↗
PubMed1985

Conditioned taste aversion to chlorpromazine, but not to haloperidol.

Using in rats a Conditioned Taste Aversion (CTA) procedure, chlorpromazine was shown to possess significant US properties at the highest dose tested (8 mg/kg IP repeated four times). In contrast, haloperidol failed to exert a similar effect at a dosage (1.6 mg/kg IP X 4) at least twice as high, in terms of pharmacological activity, as the effective chlorpromazine dosage. These data suggest that the induction of neuroleptic extrapyramidal side effects and the antidopaminergic properties shared by the two drugs may not be responsible for the aversive effect of chlorpromazine. However, it cannot be excluded than haloperidol produces an aversion which is antagonized by some action of the drug not shared by chlorpromazine.

Animals↗
PubMed1985

Influence of housing conditions and state of partner on conditioning and extinction of taste aversion to lithium and chlorpromazine.

Rats were used in two experiments to investigate the influence of social variables on the acquisition of Conditioned Taste Aversion (CTA) to either lithium chloride (10 ml/kg IP of a 0.3-M solution given twice) or chlorpromazine (8 mg/kg IP given four times) and on subsequent extinction. CTA acquisition was not affected by original housing assignment (isolation or paired housing for 15-23 days prior to conditioning), by the shifted social assignment during conditioning, or by the drugged state of the paired animals' partners on drug-scheduled days. However, for both drugs, permanently isolated animals extinguished CTA more slowly than rats housed permanently in pairs. Shifts from isolation to pairing or vice versa failed to alter CTA extinction in the case of lithium, but affected it significantly in chlorpromazine-treated rats. Shifts from isolation to paired housing with an undrugged partner produced faster extinction for lithium than the corresponding group with a drugged partner. For chlorpromazine, the effect of the same shift was exactly the opposite. Overall, the results show that changes in CTA extinction can be a function of social variables.

Animals↗
PubMed1985

Behaviorally augmented versus other components in organophosphate tolerance: the role of reinforcement and response factors.

Male Wistar-derived rats were used to assess the behaviorally augmented component of tolerance to paraoxon depression of a feeding response. Separate groups of animals were treated daily by 0.125 mg/kg of the compound given sc either 1 hr before the start or 45 min after the end of a 90-min feeding session. However, the dose was reduced to 0.0625 mg/kg from Day 9 to Day 12 of the treatment series if animals showed too severe a reduction in food consumption. After development of tolerance by the presession treatment group, the animals treated after feeding were shifted to treatment before feeding. This shift produced a marked depression in food consumption. This confirms similar data previously obtained by a different test (two-way avoidance), and indicates that behaviorally augmented tolerance to paraoxon related to practice factors may be a fairly general phenomenon. Other experiments were to assess the effects of paraoxon in the conditioned taste aversion (CTA) paradigm. These showed the development of an aversion only at high dosage levels (two pairings between the flavor cue and 0.25 mg/kg sc, or four pairings with a 0.17-mg/kg dose). However, the failure of lower doses to produce CTA may have depended on the relatively slow onset of the intoxication, producing an extended interval between the end of cue exposure and the development of malaise or illness. Two pretreatments given 6 and 3 days before the first conditioning session in an experiment using the 2 X 0.25-mg/kg schedule did not affect the development of CTA as measured by a conventional double-bottle test. However, a typical interference effect produced by prior exposure was shown by a substantial acceleration of subsequent CTA extinction in pretreated animals.

Animals↗
PubMed1983

Scopolamine and acquisition of go-no go avoidance: a further analysis of the perseverative antimuscarinic deficit.

Rats treated with scopolamine (0.5 mg/kg SC daily) during the acquisition of a discrimination task with symmetrical negative reinforcement (light-go, noise/light-no go) showed a learning impairment, with both active and passive avoidance deficits. In the initial stage of such training, however, fewer passive avoidance errors and more active avoidance errors were made by treated animals if active avoidance pretraining had occurred in the no-drug state. A similar experiment using the same stimulus arrangement with asymmetrical reinforcement (no punishment of intertrial, and no go signal, responses) showed a scopolamine effect consisting mainly of increased responding to extinction signals and during intertrial intervals, with little or no active avoidance deficit. Furthermore, interactions due to changes in treatment conditions in successive stages of training were minimized in the latter task, suggesting that the effects of the shift-no shift factor on distribution of errors in the early stages of active-passive avoidance learning were unlikely to have been due to a genuine drug dissociation. Overall, these results and others obtained previously in the same and related tasks tend to rule out some unidimensional explanations of antimuscarinic effects, e.g., response disinhibition (an exclusively motor deficit) or impairment of stimulus sensitivity (an exclusively sensory deficit). The data rather confirm the notion of a sensorimotor drug bias leading to a shift in response prepotencies depending jointly on stimuli, responses, and response consequences. Prior learning history and behavioural compensation for adverse treatment consequences at the reinforcement level may interact with the sensorimotor bias so as to produce "set perseveration" (perseveration of response tendencies).

Animals↗
PubMed1983

Discriminative stimulus properties of nicotine: further evidence for mediation at a cholinergic receptor.

Rats were trained to discriminate nicotine (0.4 mg/kg SC) from saline in a standard two-bar operant conditioning procedure with food reinforcement. The response to nicotine was dose-related and at the ED50 of 0.14 mg/kg, plasma nicotine concentrations were similar to those reported previously for cigarette smokers who inhale. The nicotine analogues anabasine and cytisine increased nicotine-appropriate responding in a dose-related manner. Animals predominantly responded on the saline-associated lever when administered drugs from a range of pharmacological classes, even at doses that were sufficiently large to reduce the overall numbers of responses. The results confirm that the nicotine discriminative stimulus is highly specific. Previous work has shown anabasine and cytisine to be active at nicotinic-cholinergic binding sites in rat brain. The finding that there is some correlation between the behavioural effects of these compounds and their actions at the nicotine binding site may indicate that the nicotine cue is mediated through a cholinergic receptor.

Animals↗
PubMed1983

Nicotine cue in rats analysed with drugs acting on cholinergic and 5-hydroxytryptamine mechanisms.

The nicotine discriminative stimulus (cue) has been used to characterize further the underlying receptor mechanisms. Rats were trained to discriminate the effects of nicotine in a standard, two-bar operant conditioning procedure with food reinforcement. Mecamylamine blocked both the discriminative effect of nicotine and the reducing effect on the response-rate. The block of the discriminative effect could not be overcome by increasing the dose of nicotine, whereas the block of the reducing effect on the response-rate could be reversed. Mecamylamine was effective when administered by either the subcutaneous or the intraventricular route, but hexamethonium was inactive by both routes. Mecamylamine, but not hexamethonium, blocked the discriminative effect of the nicotinic cholinergic agonist, cytisine. Methergoline did not block the discriminative effects of nicotine, even in doses considerably larger than those which blocked the discriminative effects of the 5-HT agonist, quipazine. Mecamylamine did not block the effects of quipazine. The results are consistent with the view that the nicotinic cue is mediated primarily through cholinergic receptors, and that 5-HT mechanisms are not involved. The block of the quipazine cue supports the view that the discriminative effects of this drug are mediated through 5-HT receptors.

Alkaloids↗
PubMed1981

Test factors affecting the time course of avoidance depression after DFP and paraoxon.

The time course of avoidance depression induced by DFP and Paraoxon in rats was measured in four experiments using sublethal doses which induced approximately equivalent changes at the time for maximal behavioral depression (3 hr after 1.1 mg/kg DPF or 0.25 mg/kg Paraoxon SC). The trends obtained with pretrained animals intoxicated for the first time, and not tested during the period between treatment and testing at any given interval (3, 8, 13, 18, and 24 hr after injection), served as baselines to assess (1) proactive consequences of one or more avoidance sessions on subsequent measurements, and (2) sensitivity changes upon repetition of treatment with the same or the other agent after a 5-week resting period. The changes in the time course of avoidance depression due to these factors were generally unimpressive. Some of the interactions observe, however, provided direct or indirect evidence (1) for an enhanced residual depression at long post-treatment intervals upon repetition of organophosphate intoxication; (2) for a proactive impairing effect sometimes appearing after behavioral testing at the time of maximal depression (3 hr), when total or near-total avoidance failure causes extensive exposure to shock; and (3) for a proactive facilitating effect sometimes appearing after testing at a time of moderate avoidance impairment (8 hr), which may be ascribed to behaviorally augmented tolerance ("learned" tolerance).

Animals↗
PubMedDate not supplied

Behaviorally augmented tolerance during chronic cholinesterase reduction by paraoxon.

Repeated injection of paraoxon to pretrained rats 2 hr before avoidance sessions, at a dose causing considerable intoxication symptoms and reduction of brain acetylcholinesterase (0.125 mg/kg SC daily), induced marked performance depression followed by progressive development of tolerance. Additional groups treated either after each session (i.e., 23.5 hr before each subsequent session), or treated and not tested, showed a substantial depression when shifted to treatment 2 hr before sessions after achievement of tolerance by the animals tested from the beginning of the experiment at the time of maximal paraoxon effect. This indicates that chronic paraoxon tolerance cannot be ascribed entirely to metabolic and/or physiological changes occurring as a consequence of repeated treatment per se, but must be explained at least in part by postulating a behaviorally augmented (or "learned") component. In an additional experiment chronic paraoxon animals (0.1 mg/kg SC daily) were indistinguishable from control rats with respect to acquisition of light/go, noise-light/no go discrimination, i.e., of an active-passive avoidance task known to be highly sensitive to the disrupting (response-disinhibiting) effect of antimuscarinics. Therefore, the enhanced sensitivity to antimuscarinics in organophosphate tolerant rats, which is usually ascribed to cholinergic receptor changes, does not appear to be associated with a spontaneous "antimuscarinic-like" syndrome.

Animals↗