8-OH-DPAT inhibits both prandial and waterspray-induced grooming.

The effects of 8-OH-DPAT treatment on rat grooming behaviour, elicited either prandially or in response to spraying with water were investigated. Dose (< or =0.1 mg/kg s.c.) response studies employed momentary time sampling over 30 or 60 min with behaviour being scored in one of 6 or 7 (depending on food availability) mutually exclusive categories (feeding, active, scratching, face-grooming, body grooming, genital-grooming and resting) at 15 s intervals. In non-deprived rats, tested with wet mash available, feeding and activity frequencies were increased, but resting and total grooming were inhibited by 8-OH-DPAT. Face-, body- and genital-grooming occurred at higher levels than scratching, but all categories were reduced with reductions in scratching occurring at a lower dose (0.01 mg/kg). Misting rats with a fine water spray selectively increased body grooming and decreased activity without altering feeding, while 8-OH-DPAT increased feeding and reduced face-, body- and genital-grooming, without affecting already low levels of scratching. In misted rats, tested without food, 8-OH-DPAT reduced face-, body- and genital-grooming and increased resting. These results confirm i) that the water spray technique is a useful method for increasing grooming and ii) that 8-OH-DPAT has a suppressant effect on grooming independent of response competition from enhanced feeding.

Subjective self-control and behavioural impulsivity coexist in anorexia nervosa.

OBJECTIVE: Anorexia nervosa (AN) has been associated with impulse regulation problems. This study investigated subjective and behavioural impulsivity in women with anorexia nervosa (n=15) and a control group (n=16). METHOD: A self-report measure (the impulsiveness, venturesomeness, and empathy questionnaire; I(7)) and two behavioural measures (a continuous performance task [CPT]; and a novel risk taking measure [Bets 16]) of impulsivity were used along with the Beck Depression Inventory (BDI). RESULTS: The AN group had elevated BDI scores and lower self-reported impulsiveness and venturesomeness scores, but they also displayed impulsive behaviour on the CPT (more errors of commission with faster reaction times). DISCUSSION: The coexistence, in AN, of self-reported self-control and behavioural impulsivity indicates that the relationship between impulsivity and disordered eating in AN is more complex than previously recognised and supports the view that self-awareness in AN is low.

Impulsivity, risk taking and recreational 'ecstasy' (MDMA) use.

The present study investigated characteristics of recreational drug users, especially 'ecstasy' (MDMA) users, in 254 undergraduates. All participants completed a drug history questionnaire (DHQ), the impulsiveness venturesomeness and empathy questionnaire, a novel risk-taking task (Bets16), and 59 also completed the tri-dimensional personality questionnaire (TPQ). DHQ responses allocated participants to five groups: non-drug controls, cannabis users, polydrug (no ecstasy) users, low (<20 occasions) ecstasy users and high (>20 occasions) ecstasy users. Eighteen percent of the sample had used ecstasy and of the ecstasy users, only one had not used other substances. A larger proportion of high ecstasy users had also used amphetamines, cocaine and LSD in comparison to the low ecstasy and non-ecstasy polydrug users. High ecstasy users typically took significantly more ecstasy tablets compared with low ecstasy users. Impulsiveness, venturesomeness and novelty seeking behaviour increased from the non-drug users to high ecstasy users. Ecstasy users (low and high) and polydrug (non-ecstasy) users had higher levels of impulsivity, venturesomeness and novelty seeking behaviour compared with non-drug users. Furthermore, high ecstasy users scored higher on the Bets16 risk-taking measure than non-drug users, cannabis users and low ecstasy users. The findings are discussed in relation to: (i) the possibility that increased impulsivity pre-dated drug use; and (ii) the possible link between impulsivity and the putative serotonergic neurotoxicity of ecstasy.

Alpha2-adrenoceptor antagonism is neither sufficient nor necessary for the distinctive action of atypical neuroleptics on intracranial self-stimulation in the rat.

Response rates in variable-interval intracranial self-stimulation (ICSS) in rats can provide a continuous record of drug-induced changes in brain function. Use of this procedure has been found to distinguish between typical and atypical neuroleptics, with the latter producing a similarly intense but much briefer depression of responding. This difference has been ascribed to the alpha2-adrenoceptor antagonist properties of atypical neuroleptics, but the evidence is ambiguous. The role of alpha2-adrenoceptors was examined in the present study using ventral tegmental ICSS to track the depressant effects of the typical and atypical neuroleptics, haloperidol (0.075 mg/kg) and olanzapine (0.9 mg/kg), injected alone or in combination with an alpha2-adrenoceptor agonist or antagonist. Neither haloperidol nor olanzapine (despite its atypical features) shows appreciable affinity for the alpha2-adrenoceptor. In the present study, olanzapine was found to depress self-stimulation responding dose-dependently, but with considerable recovery after 4 h. Simultaneous administration of alpha2-adrenoceptor receptor agonists or antagonists (respectively clonidine 0.015 mg/kg or idazoxan 3.0 mg/kg) failed significantly to increase or decrease the action of either haloperidol or olanzapine. These results indicate that alpha2-adrenoceptor antagonism does not necessarily promote recovery from neuroleptic-induced depression, and that 'atypical' features do not necessarily depend on alpha2-adrenoceptor antagonism. Various other explanations remain possible, but the accelerated time course of the atypical agents appears to support more recent explanations, based on their rapid dissociation from the D2 receptor.

Tolerance and sensitization to stimulant and depressant effects of nicotine in intracranial self-stimulation in the rat.

Nicotine is thought to be an important factor in addiction to tobacco but its psychopharmacological properties are still uncertain. In the present study, rats were trained to operate a pedal to obtain threshold-current, variable-interval hypothalmic stimulation. Response rates were printed out at 10min intervals to provide a continuous record of facilitatory or depressant effects by injected nicotine. Responding was enhanced in all rats but this depended on dose, time after injection, and previous exposure to the drug. In the first 10min after injection, responding by drug-naive rats was either unaffected (40-130mg/kg s.c., as base) or strongly depressed (400µg/kg). This phase was followed by prolonged (>50min) dose-dependent facilitation. Higher doses (1.3mg/kg) caused prostration. Chronic exposure to nicotine (400µg/kg x 10 at 2-5 day intervals) reduced the initial depressant effect; it also augmented subsequent responding, but only in the early minutes after injection; the latter finding indicates that apparent sensitization to chronic nicotine may depend primarily on tolerance to its depressant effects, rather than on receptor upregulation. Stimulant and depressant effects of nicotine were prevented by pretreatment with the centrally acting antagonist, mecamylamine (2.0mg/kg s.c.), but not by the peripheral antagonist, hexamethonium (1.0mg/kg s.c.) or by the muscarinic receptor antagonist, hyoscine (scopolamine; 100-300µg/kg s.c.). Self-stimulation was unaffected by mecamylamine alone. Thus the inhibitory action of nicotine is unlikely to be due to depolarization block, peripheral activity or muscarinic activity. Its facilitatory and depressant effects appear to be narrowly time- and dose-specific, thus accounting for divergent findings in many studies.

Unusual interactions between the neuroleptic haloperidol, and the dopamine D2 partial agonist, terguride.

Terguride is an ergoline derivative which has been reported to act as a partial agonist at central dopamine D2 receptors. Depending on the state of the receptor, terguride may resemble an agonist or an antagonist in its pharmacological effects. The present study investigated interactions of terguride with the dopamine D2 antagonist haloperidol in the rat. Terguride (0.025 mg/kg, i.p.) lowered, whereas haloperidol (0.025 mg/kg, s.c.) increased serum prolactin levels. When given together there was a tendency for prolactin to be lowered, i.e. terguride fully antagonized the action of haloperidol. Both terguride and haloperidol dose-dependently reduced locomotor activity, with terguride being at least 50 times more potent. However, in the presence of a subthreshold dose of haloperidol (0.1 mg/kg), terguride was effective in reducing locomotor activity. Terguride and haloperidol were equally potent in disrupting performance of lever pressing for food on a VI 120 sec schedule (ED(50) values 0.22 and 0.28 mg/kg, respectively). When given together, there was a statistically significant interaction; a terguride dose of 0.2 mg/kg lowered rates of lever pressing when given with vehicle or a low (0.03 mg/kg) haloperidol dose, but antagonized the effect of 0.3 mg/kg haloperidol. Terguride dose-dependently disrupted lever pressing for intracranial stimulation reward (ED(50) value approx. 0.3 mg/kg). Haloperidol (0.26 mg/kg) also disrupted lever pressing but the two drugs together showed no greater effect than haloperidol alone. These observations are discussed in the context of terguride's suggested partial agonistic properties.