Novelty-induced place preference behavior in rats: effects of opiate and dopaminergic drugs

In Experiment 1, adult male rats were given eight 30-min exposures to one of two distinct environments. Control animals received either four exposures to each environment or were not exposed to either environment. When given free-choice access to both environments simultaneously, animals spent significantly more time in the novel environment relative to the familiar environment. In these same animals, horizontal and vertical activity rates were lower in the novel environment than in the familiar environment. In Experiments 2-5, animals were assessed for novelty preference behavior under the influence of either morphine (0, 0.1, 0.3, 1.0 or 3.0 mg/kg), naltrexone (0, 0.1, 0.3 or 1.0 mg/kg), amphetamine (0, 0.1, 0.3 or 1.0 mg/kg) or haloperidol (0, 0.03, 0.1, 0.3 or 1.0 mg/kg). Haloperidol produced a dose-dependent disruption in novelty preference behavior, while all other drugs tested were without effect. Haloperidol also disrupted the novelty-induced decrease in horizontal and vertical activity rates. These results suggest that haloperidol blocks the reinforcing and locomotor-depressant effects of a novel environment in a free-choice preference test.     

Disruption of selective attention by apomorphine,but not amphetamine,in the mongolian gerbil

To test the hypothesis that apomorphine, but not amphetamine, disrupts selective attention to a novel stimulus, gerbils were exposed to a novel object for one 60-s trial following an injection of 0, 1, 3, or 6 mg/kg d-amphetamine base, or 0, 0.1, 0.3, 1, 3, or 10 mg/kg apomorphine HClSC. They were tested the next day for habituation to the stimulus. As a control, half of each group of gerbils were injected but not exposed to the object on day 1. All non-exposed gerbils and all exposed gerbils that received amphetamine showed a decrement in investigation, indicative of habituation, on day 2. Furthermore, a gradient of responding during dishabituation was obtained from gerbils given d-amphetamine (1 mg/kg) which was dependent on the distance a novel object was moved, indicating a perception of location as occurs in normal gerbils. In contrast, those exposed gerbils that received 1 mg/kg or more of apomorphine did not show habituation on day 2. That the disruption of habituation by apomorphine was due to a failure of input rather than of retrieving the information was demonstrated in an experiment in which two groups of gerbils were habituated to a novel object prior to injection with apomorphine (1 mg/kg) or saline. Both groups continued to show habituation on subsequent trials and increased responding when the object was moved. Thus, the motor capabilities necessary for investigation were functional. When gerbils that received apomorphine were pretreated with the dopamine receptor blocker pimozide, habituation occurred on day 2, suggesting that the disruption of habituation was mediated by dopamine. On the other hand, the depressant effect of large doses of apomorphine on initial investigation was not blocked completely by pimozide.     

Effects of GABA-ergic drugs on penile erection induced by apomorphine in rats

The effects of GABA agonists and antagonists on penile erection (PE) induced by apomorphine were investigated in rats. Subcutaneous (SC) administration of apomorphine (0.01–0.1 mg/kg) induces a dose-dependent PE in rats. The maximum effect was obtained with 0.1 mg/kg of the drug. The response was decreased with increasing doses of apomorphine from 0.1 to 0.5 mg/kg. The response induced by apomorphine (0.1–0.5 mg/kg) was decreased in animals pretreated with either the GABA-A agonist muscimol or the GABA-B agonist baclofen. Combination of muscimol with baclofen caused a stronger inhibitory effect on apomorphine-induced PE. Bicuculline or picrotoxin but not phaclofen reduced the inhibitory effect of muscimol on PE induced by apomorphine, whereas phaclofen but not GABA-A antagonists decreased the inhibitory action of baclofen on apomorphine-induced PE. Pretreatment of animals with higher doses of the GABA-A antagonists bicuculline and picrotoxin or the GABA-B antagonist phaclofen elicited inhibition of apomorphine-induced PE. However, the inhibitory effects of GABA-A and GABA-B antagonists are lost on combination. Administration of GABA-A and GABA-B receptor stimulation inhibit PE induced by dopaminergic mechanism(s).     

Agmatine potentiates morphine-induced conditioned place preference in mice: modulation by alpha2-adrenoceptors.

The effects of agmatine, an endogenous polyamine metabolite formed by decarboxylation of L-arginine, and its combination with morphine on conditioned place preference (CPP) has been investigated in male mice. Our data show that subcutaneous administration of morphine (1-7.5 mg/kg) significantly increases the time spent in the drug-paired compartment in a dose-dependent manner. Intraperitoneal administration of agmatine (1-40 mg/kg) alone does not induce either CPP or conditioned place aversion, while combination of agmatine and subeffective doses of morphine leads to potent rewarding effects. Lower doses of morphine (0.1, 0.05, and 0.01 mg/kg) are able to induce CPP in mice pretreated with agmatine 1, 5, and 10 mg/kg, respectively. Concomitant intraperitoneal administration of UK 14 304 (0.5 mg/kg), a highly selective alpha2-agonist, with per se noneffective dose of morphine (0.5 mg/kg) and also its combination with noneffective doses of agmatine (1 mg/kg) plus morphine (0.05 mg/kg) produces significant CPP. UK 14 304 (0.05, 0.5 mg/kg) alone, or in combination with agmatine (1, 5 mg/kg) have had no effect. We have further investigated the possible involvement of the alpha2-adrenoceptors in the potentiating effect of agmatine on morphine-induced place preference. Selective alpha2-antagonists, yohimbine (0.005 mg/kg) and RX821002 (0.1, 0.5 mg/kg), block the CPP induced by concomitant administration of agmatine (5 mg/kg) and morphine (0.05 mg/kg). Yohimbine (0.001-0.05 mg/kg) or RX821002 (0.05-0.5 mg/kg) alone or in combination with morphine (0.05 mg/kg) or agmatine (5 mg/kg) fail to show any significant place preference or aversion. Our results indicate that pretreatment of animals with agmatine enhances the rewarding properties of morphine via a mechanism which may involve alpha2-adrenergic receptors.     

The effects of apomorphine on leverpress shock escape learning in rats

Four groups of rats (n = 10 each) were tested on a discrete trial leverpress shock escape task 15 min following an intraperitoneal injection of either 0 (saline), 0.5, 1.0, or 2.0 mg/kg apomorphine hydrochloride. The results indicated that all doses of apomorphine produced a severe disruption in escape performance. This disruption was temporary, however, as all apomorphine groups were responding as quickly as the saline control rats by the end of the training session. A comparison of the effects of apomorphine with the previously reported effects of scopolamine and septal lesions on shock escape learning revealed both similarities and differences. These findings suggest that a septal lesion-induced reduction of acetylcholine levels does not simply "unleash" an antagonistic dopaminergic system.     

Role of training dose in discrimination of nicotine and related compounds by rats

Rats were trained to discriminate nicotine from saline in a two-bar operant conditioning procedure with food reinforcement. There was partial generalization to the nicotine analogues anabasine and cytisine in rats trained to discriminate either 0.2 or 0.4 mg/kg nicotine from saline. However, generalization was complete in rats trained to discriminate 0.1 mg/kg nicotine and, in a novel procedure, any one of three doses of nicotine (0.1, 0.2, or 0.4 mg/kg). There was no generalization to the muscarinic-cholinergic agonist oxotremorine (0.0025–0.04 mg/kg). Additional experiments were carried to further characterize the response of rats trained with nicotine (0.1 mg/kg). These animals failed to generalize to compounds from a range of pharmacological classes (i.e., apomorphine, cocaine, chlordiazepoxide, picrotoxin, and quipazine), but there was partial generalization to amphetamine. Mecamylamine (0.5 mg/kg) but not hexamethonium (5.0 mg/kg) blocked the discrimination of nicotine and the generalization to cytisine. Anabasine (1.0–4.0 mg/kg) did not block the response to nicotine. The results support the view that the nicotine cue is mediated mainly through central cholinergic mechanisms. The dose of nicotine used for training has a very significant influence on the characteristics of the cue and 0.1 mg/kg of nicotine may be more suitable than 0.4 mg/kg as a training dose in future work.     

Pharmacology of sucrose-reinforced place-preference conditioning: effects of naltrexone

Two experiments investigated the role of the opioid system in sucrose-reinforced conditioned place preferences (CPPs) in rats. Experiment 1 examined the effects of a general opioid antagonist, naltrexone, on the expression of a CPP acquired in the absence of the drug. Subjects were trained to associate one compartment of a two-compartment chamber with sucrose and the other compartment with water. Rats displayed a preference for the sucrose-associated compartment in a choice test without sugar or water available following vehicle saline treatment. Naltrexone doses of 2.5 and 5.0 mg/kg reduced this preference for the sucrose-associated compartment. Experiment 2 examined the effects of naltrexone on the acquisition as well as the expression of CPPS. Different groups of rats received daily injections of either saline, 0.1, 1.0, or 5.0 mg/kg of naltrexone prior to each training session, and then these groups were given a choice test for the CPP after saline or naltrexone injections. Although naltrexone treatment attenuated the expression of CPPs in each group relative to saline treatment, there were no group differences during these tests in the magnitude of the preferences. Moreover, all groups displayed equal acquisition of CPPs despite the fact that naltrexone dose dependently decreased sucrose intake during the training phase. Together, the results indicate that the opioid system modulates the expression but not the acquisition of sucrose-reinforced CPPs.     

Reversal of stress-induced analgesia by apomorphine,but not by amphetamine

Acute exposure to severe stressors induce profound analgesia as well as depleting catecholamine levels. The present study examined whether d-amphetamine and apomorphine, agents which increase catecholamine availability, would alter the analgesic effectiveness of cold-water swims (CWS) and 2-deoxy-D-glucose (2-DG) as measured by an operant liminal escape procedure. Two groups of 10 rats each were tested to determine alterations in liminal escape threshold functions following amphetamine at doses of 0.25, 0.5, 1,2 mg/kg and following apomorphine at doses of 0.025, 0.05, 0.1, 0.2 mg/kg. Half of the amphetamine and half of the apomorphine groups were tested across their respective dose ranges for the drug effects upon CWS analgesia. The remaining animals in each group received 2-DG (600 mg/kg IP) alone followed by 2-DG paired with each stimulant dose. No dose of amphetamine or apomorphine alone altered escape thresholds. While amphetamine produced slight potentiations of 2-DG analgesia at the two low doses, apomorphine at the 0.05 and 0.1 mg/kg doses returned CWS and 2-DG analgesia to within normal placebo values. These results provide indirect evidence for a role for brain norepinephrine and dopamine in stress-induced analgesia, and these data are discussed with respect to catecholamine involvement in pain-inhibitory processes.     

Cocaine, but not alcohol, reinstates cocaine-induced place preferences

Alcohol has been reported to modulate the reinforcing and aversive properties of cocaine. Given these effects, the present study examined whether this interaction could be extended to cocaine seeking using the conditioned place preference (CPP) procedure. Specifically, 31 drug-naive, male Sprague-Dawley rats were injected every other day (for 8 days) with either 20 mg/kg cocaine or vehicle in an alternating sequence prior to being restricted to a drug or vehicle side of a place preference chamber for 30 min. On Day 9, subjects were given 15-min access to the entire chamber to assess compartment preference. Animals then underwent extinction by pairing both compartments with vehicle for an additional 8 days. Extinction was assessed in the same manner as place conditioning. The animals were then given priming injections of vehicle, 15 mg/kg cocaine, 0.5 or 1.0 g/kg alcohol on the day following the extinction test. Pairing 20 mg/kg cocaine with a specific compartment resulted in a significant place preference. Breaking the relation between the compartment and the drug by pairing both compartments with vehicle extinguished this preference. Interestingly, only 15 mg/kg cocaine was able to reinstate the cocaine-induced place preference, suggesting that the ability to reinstate cocaine seeking may be drug specific.     

The effects of selective dopamine D1 or D2 receptor antagonists on the establishment of agonist-induced place conditioning in rats

The ability of the dopamine D1 antagonist, SCH 23390 (0.01, 0.1, 1.0, 2.0 mg/kg) or the D2 antagonist, metoclopramide (1.0, 10.0, 20.0 mg/kg), to block the establishment of place conditioning with either the nonselective dopamine agonist, amphetamine (2.0 mg/kg), the D1 agonist, SKF 38393 (10.0 mg/kg), or the D2 agonist, quinpirole (1.0 mg/kg), was evaluated in rats. The experimental protocol consisted of three phases. During the preexposure phase, rats explored two distinctive compartments joined by a small tunnel. During the 8-day conditioning phase, rats were pretreated with either saline, SCH 23390 or metoclopramide; 1 hr later the animals were treated with an agonist and confined to one compartment for 30 min. On alternate days, rats received saline and were placed in the opposite compartment. Test days occurred over the remaining 3 days during which drug-free animals were allowed access to both compartments. A significant increase or decrease in the amount of time spent in the drug-paired environment was indicative of a place preference or aversion, respectively. SCH 23390 and metoclopramide were effective in blocking amphetamine-induced place preference and SKF 38393-induced place aversion. At lower doses, the D1 and D2 antagonist blocked the place preference induced by quinpirole, however, higher doses were not effective. In general, these data suggest that both receptor subtypes participate in the establishment of place conditioning with amphetamine, SKF 38393 or quinpirole.     

Interaction of buspirone and dopaminergic agents on punished behavior of pigeons

The non-benzodiazepine anxiolytic buspirone was studied alone and in combination with either haloperidol or apomorphine. Drug effects were evaluated under a baseline of punished and unpunished keypeck responses of pigeons; every 30th response produced food (no punishment) in the presence of a white keylight and, when the keylight was red in alternate 3 min periods, every 30th response produced both food and a brief electric shock (punishment). Buspirone (0.03-3 mg/kg, IM) increased the low rates of punished responding to a maximum of 1000% of control at doses of 0.1-1 mg/kg. Unpunished responding was only marginally affected at lower doses and dose-dependent decreases were obtained from 1 to 10 mg/kg. Although less potent, chlordiazepoxide (1-100 mg/kg IM) produced effects which were similar to those of buspirone, a finding which contrasts with the greater efficacy of benzodiazepines for increasing punished behavior in mammals. Dose-effect functions for buspirone were unchanged by haloperidol administration (0.01 and 0.03 mg/kg, IM, 5 min prior) or by concurrent treatment with a behaviorally-ineffective dose of apomorphine (0.003 mg/kg, IM). Rate-decreasing doses of apomorphine (0.01-0.1 mg/kg) reversed the increases in punished responding produced by lower doses of buspirone (0.03 and 0.1 mg/kg) and the apomorphine-induced decreases in unpunished responding were antagonized by buspirone at doses which had little affect when given alone. The ability of buspirone to reverse the rate-decreasing effects of apomorphine on unpunished responding suggests that buspirone does exhibit dopaminergic antagonist properties in vivo. However, effects of buspirone on punished responding of pigeons do not appear to be due to dopaminergic mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)     

The delayed effects of DTG and MK-801 on latent inhibition in a conditioned taste-aversion paradigm

The delayed effects of phencyclidine (PCP) have been shown to disrupt latent inhibition (LI) in a conditioned taste-aversion paradigm. In an attempt to understand the mechanism of this disruption, the delayed effects of the selective sigma receptor agonist 1,3-Di(2-tolyl)guanidine (DTG) and the selective NMDA receptor antagonist MK-801 on latent inhibition were assessed in the same paradigm. Water-deprived male rats were allowed access to either water (nonpreexposed; NPE) or 5% sucrose (preexposed; PE) for 30 min on 2 consecutive days. On the third day, animals were allowed access to sucrose and subsequently injected with lithium chloride. On the forth day, animals were allowed access to both sucrose and water. LI was assessed by comparing the percent sucrose consumed in PE and NPE groups on the fourth day. DTG (1.0, 5.0, or 10.0 mg/kg), MK-801 (0.5, 1.0, or 2.0 mg/kg), or vehicle was administered IP 20 h before preexposure (days 1 and 2) and conditioning (day 3). In vehicle-treated groups, PE animals consumed a significantly higher percent sucrose on the test day than NPE animals, indicating the presence of LI. DTG (10.0 mg/kg) and MK-801 (2.0 mg/kg) decreased the percent sucrose consumed by animals in the PE group to the level observed in the NPE group, indicating disrupted LI. However, this dose of MK-801 was found to produce a decrease in percent sucrose consumed in PE animals not treated with lithium chloride, indicating that the decrease observed in the LI paradigm could be due to MK-801-induced decrease in taste preference for sucrose rather than a disruption of LI. Lower doses of MK-801 that did not produce a decrease in taste preference for sucrose did not significantly disrupt LI. None of the doses of DTG tested altered taste preference for sucrose. These data suggest a role for sigma receptors in the previously observed PCP-induced disruption of LI. Published by Elsevier Science Inc., 2000     

Effects of chronic lithium pretreatment on apomorphine-induced penile erection

• 1.1. The effects of chronic lithium pretreatment (600 mg/l in drinking rats, 30 days) on penile erection (PE) induced by apomorphine were investigated in rats. This treatment resulted in a serum Li concentration after 30 days of 0.31 ± 0.01 mmol/l.
• 2.2. Subcutaneous (s.c.) administration of mixed Dl/D2 dopamine receptor agonist apomorphine (0.05–0.5 mg/kg) induced PE in a biphasic manner. The maximum effect was obtained with 0.1 mg/kg of the drug while the response decreased with increasing doses of apomorphine from 0.1 to 0.5 mg/kg.
• 3.3. Pretreatment of animals with 0.0125-0.1 mg/kg of D1 dopamine receptor antagonist SCH 23390 or D2 dopamine receptor antagonist sulpiride (12.5–100 mg/kg) decreased apomorphine-induced PE. Combination of SCH 23390 (0.025 mg/kg) with sulpiride (12.5 mg/kg) caused a stronger inhibitory effect on apomorphine response. This indicates that both D1 and D2 dopamine receptors may be involved in PE induced by apomorphine.
• 4.4. The response induced by apomorphine (0.05-0.5 mg/kg) was decreased in animals pretreated with chronic lithium. The inhibitory effect of sulpiride on apomorphine response, increased in animals pretreated with lithium, in contrast the inhibitory effect of SCH 23390 did not change in this condition. However, a combination of SCH 23390 with sulpiride increased inhibitory effect on apomorphine response in lithium pretreated rats.
• 5.5. It is concluded that chronic lithium inhibits PE induced by dopaminergic mechanism(s).

     

Behavioral response to apomorphine and its interaction with opiates in domestic pigeons

Domestic pigeons received peripheral injections of saline or the dopamine agonist apomorphine (AM) at doses of 0.025, 0.05, 0.1, 0.25, 0.5 or 1 mg and their behavior was studied for 30 min after these treatments. Given at a dose of 0.025 mg, AM decreased pecking, whereas doses ranging from 0.1 to 1 mg strongly stimulated this behavior. The frequency of headshaking was enhanced by the administration of each dose of AM; at the 3 higher doses, the drug also attenuated the frequency of preening. In another experiment, AM was administered 40 min after the injection of either naloxone (0.5, 1 or 4 mg), the opiate agonist levorphanol (0.25, 0.5 or 1 mg) or its dextroisomer, dextrorphan (0.25, 0.5 or 1 mg), while the birds were observed as before. No interaction between AM and either naloxone or dextrorphan was detected. By contrast, injection of each dose of levorphanol attenuated preening, and completely antagonized the stimulating effect of AM treatment on headshaking. At a dose of 1 mg, levorphanol also slightly decreased the frequency and increased the latency of occurrence of pecking. It is concluded that in pigeons, opiates modulate the behavioral response to apomorphine in a complex fashion.     

Apomorphine-induced motor behavior in rats exposed prenatally to alcohol

We psychopharmacologically examined dopamine function in rats exposed to ethanol prenatally. Pregnant rats received liquid diets of 35% or 0% ethanol-derived calories (EDC), or ad lib lab chow (LC). Twenty-eight-day-old offspring received systemic doses of apomorphine chosen to stimulate predominantly presynaptic (0.02 or 0.1 mg/kg) or postsynaptic dopamine receptors (2.0 or 5.0 mg/kg). Behavior was scored automatically for 60 min in an "open field." For males, prenatal ethanol exposure resulted in a dose-response shift to the left for locomotor activity. Females exposed to the liquid diet, with or without ethanol, showed less of an increase in locomotor activity following the 5.0 mg/kg dose of apomorphine than did LC controls. There were no effects of prenatal treatment on repetitious motor behavior in the automated "open field" or on stereotypy scored by direct observation in separate groups of rats. The results are consistent with an hypothesis that prenatal ethanol exposure alters the sensitivity of postsynaptic (perhaps mesolimbic) dopamine systems important to locomotor activity in young male rats.     

Further studies on nicotine-induced conditioned place preference in the rat

Rats received subcutaneous (SC) injections of either nicotine (NIC, 0.001 to 2.0 mg/kg) or saline (SAL, 1 ml/kg) immediately prior to conditioning sessions in a conditioned place preference (CPP) paradigm. NIC was paired for 3 conditioning sessions with one environment of a 3 compartment CPP apparatus; SAL was paired with another environment. The animals were then tested for place preference by determining the proportion of time spent in each compartment during a 15 min test session. A dose-response curve was obtained for the place conditioning effect of nicotine as measured by its ability to alter baseline preferences calculated from control rats. NIC's place preference, but not place aversion, effect was linearly correlated with respect to dosage within the range of 0.1 to 0.8 mg/kg. NIC, 0.8 mg/kg, induced a place preference when it was administered immediately prior to conditioning sessions, but not when administered 20, 60 or 120 min prior to the sessions. Three repeated conditioning and testing cycles, or the daily administration of NIC for 2 weeks between conditioning and testing cycles had little or no effect on NIC place conditioning. Lobeline (2, 10 and 20 mg/kg) or cotinine (1 to 50 mg/kg) failed to condition a place preference. NIC, 0.1 or 1.2 mg/kg SC, administered to rat pups on postnatal days 5 through 8, did not alter subsequent place preference (induced by 0.8 mg/kg of NIC) measured at approximately 40 and 70 days of age. Periodic measurements of spontaneous motor activity, forelimb grip strength and negative geotaxis were unaltered by the perinatal exposure to nicotine.     

Diazepam-induced place preference conditioning: Appetitive and antiaversive properties

The place conditioning paradigm was used to examine the reinforcing properties of diazepam. Rats were injeccted with diazepam (0.5–5.0 mg/kg, IP) and 30 min later were confined for 30 min to one side of a shuttle box, in which each of the two compartments had distinctive features. On alternate (control) days they received vehicle injections and were confined for 30 min to the opposite side. At almost all doses tested, diazepam produced place preference for the distinctive compartment that had been previously associated with the drug. Preference for the drug side developed regardless of whether diazepam was paired or unpaired with the least-preferred side, and regardless of whether testing was carried out in the undrugged or in the drugged state. The rats preferred the drug side over a novel compartment, but they did not change their initial preference for the side when diazepam was given after removal from the training box.Animals injected with meprobamate (70 mg/kg, PO), a non-benzodiazepine anxiolytic, also developed conditioned preference for the drug side, comparable to that seen following cocaine hydrochloride (10 mg/kg, IP).The diazepam (2.5 mg/kg)-induced place preference was antagonized by CGS 8216 (3 mg/kg, IP), picrotoxin (2 mg/kg, IP) and naloxone (0.8 mg/kg, SC), injected 3 min before and 15 and 20 min after diazepam respectively. Sodium valproate (200 mg/kg, IP) did not influence diazepam (1 mg/kg)-induced place preference. Sodium valproate by itself had marginal effects on place conditioning. Picrotoxin and naloxone, but not CGS 8816, produced place aversion which, in the case of picrotoxin, was due to state dependent learning. The results provide a clear indication that the place preference paradigm is valid as a test for evaluating appetitive properties of minor tranquilizers. They suggest that the rewarding effects of diazepam are mediated through central benzodiazepine receptors. Wheter GABA and/or endogenous opioid peptides are involved in the reinforcing properties of diazepam remains an open question.A preliminary report of this research was made at the 14 C.I.N.P. Congress (Florence 1984)     

Effect of nicotine on sniffing induced by dopaminergic receptor stimulation.

Effects of nicotine on sniffing induced by amphetamine and apomorphine have been tested in rats. Intraperitoneal (i.p.) administration of nicotine (0.5 and 1 mg/kg), amphetamine (1-6 mg/kg) or apomorphine (0.1-1 mg/kg) induced sniffing. Nicotine (0. 25-1 mg/kg) potentiates sniffing induced by amphetamine (1 mg/kg). Nicotine (1 mg/kg) also potentiates the response induced by different doses (0.1-1 mg/kg) of apomorphine. Atropine induced sniffing and increased the response of both amphetamine and nicotine. Higher doses of hexamethonium decreased the sniffing response induced by amphetamine and the response induced by combination of amphetamine and nicotine. Sulpiride reduced the response induced by nicotine or amphetamine plus nicotine, while SCH23390 reduced normal sniffing behaviour of the animals and sniffing induced by either amphetamine or amphetamine plus nicotine. The data may indicate that nicotinic receptor mechanism(s) may be involved in the sniffing induced by dopaminergic receptor stimulation.     

Novelty preference predicts place preference conditioning to morphine and its oral consumption in rats

Sensation seeking is frequently observed among drug addicts. This behaviour has been modelled in non-primate animals as novelty seeking. We previously determined that novelty preference did not predict amphetamine-induced place conditioning but was positively correlated with the consumption of a low concentrated amphetamine solution. Here, we studied the relationship between novelty seeking and the vulnerability to rewarding and reinforcing effects of morphine. Wistar rats were selected according to their novelty preference. In this model, animals have free choice between a new compartment and a "familiar" compartment to which they were previously exposed during two 30-min sessions, 24 h apart. We measured oral morphine consumption when this drug was presented in tap water (25 or 50 mg/l) in free choice with water or when it was presented (50 mg/l) in a 5% (w/v) sucrose solution in free choice with a sucrose solution. The oral consumption of quinine was also measured. The rewarding effect of morphine (1.25 and 5 mg/kg; i.p.) was determined in a conditioned place preference paradigm. Whereas high and low novelty seekers did not differ in reactivity to the aversive taste of quinine, preference for novelty was associated with a greater oral morphine consumption as well as an increased conditioned place preference induced by the 5 mg/kg dose of morphine. The present results support the hypothesis that novelty preference predisposes to drug abuse.     

Differential effects of haloperidol and clozapine on attention

Haloperidol (0, 0.1, 0.3, or 1.0 mg/kg), the typical butyrophenone neuroleptic, decreased investigation of novel objects by gerbils following systemic injections. When given prior to apomorphine (1 or 3 mg/kg), haloperidol blocked apomorphine-induced disruption of selective attention in a dose-dependent manner. Thus, haloperidol acts like pimozide in this paradigm. In contrast, clozapine (0, 0.03, 0.1, 0.3, 1.0, or 3.0 mg/kg), the atypical dibenzodiazepine neuroleptic, increased frequency of investigation both soon after injection and 24 h later, suggesting interference with maintenance of attention. When given with apomorphine (1.0 mg/kg), clozapine did not block apomorphine effects on selective attention. The results are related to differential effects of these neuroleptics on other behaviors and to their individual pharmacological profiles.