Factors associated with HCV test uptake in heroin users entering substitution treatment in Greece.

OBJECTIVES: People who inject drugs (PWID) represent the main risk group for hepatitis C virus (HCV) infection in most middle and high-income countries. Testing PWID is considered as an important prevention measure. Identification of PWID characteristics associated with HCV testing may contribute to strategies targeting the containment of the HCV and HIV epidemics in Greece. METHODS: Anonymous behavioural data from 2747 heroin users were collected upon entry in 38 opioid substitution treatment (OST) clinics in Greece during the period 2013-2015. HCV test uptake was the dependent variable while covariates included sociodemographic and addiction-related variables, mostly derived from the EMCDDA treatment demand indicator protocol. RESULTS: Among 2299 cases with complete data on HCV testing, 83.5% reported any HCV testing uptake, with 61.2% reporting a recent test (< 12 months). In the multivariate analyses, any previous HCV testing uptake was associated with age ≥ 25 years, past drug treatment attempt, injecting or sniffing the primary substance, injection history ≥ 5 years, and syringe sharing earlier than the past 12 months. Past HCV test uptake was higher among those reporting full-time employment and 2-4 years injecting histories, and lower among residents of Athens. Recent testing was positively associated with female gender and polysubstance use. CONCLUSION: Any previous HCV testing uptake is high among PWID entering OST in Greece and is associated with older age, longer injecting histories and past drug-related treatment attempts. Efforts to prevent and mitigate the ongoing HCV test epidemic among PWID in Greece should combine treatment with scaling up of screening, targeting especially those younger than 25 years and at the beginning of their hazardous use.

D-amphetamine, cocaine and caffeine: a comparative study of acute effects on locomotor activity and behavioural patterns in rats.

Although open-field behaviour has been considered a valid and reliable index of locomotor activity in rodents, the simple measures traditionally recorded in this test do not readily allow for differentiation between compounds of the same general class, e.g. psychostimulants. The present methodology was developed to facilitate detailed and continuous observations on the behaviour of drug-treated rats. In addition to an automated (photocell) measure of general locomotor activity, ethological techniques were used to record the frequency and duration of standing, moving, sniffing, rearing, grooming, scratching, sniffing air, freezing, head-swinging and licking. A series of factor analyses was also performed in order to further characterize treatment-induced changes in the structure of behaviour. Compounds studied were d-amphetamine (0.5, 1.5, 3, 6 mg/kg), cocaine (5, 10, 20, 50 mg/kg) and caffeine (5, 10, 20, 40 mg/kg). Although all three psychostimulants increased the automated measure of general locomotor activity, cocaine (which produced the largest effects) monotonically increased general activity over the dose range tested, whereas the stimulant effects of the other two compounds were either reduced (d-amphetamine) or eliminated (caffeine) at higher doses. More detailed observations provided confirmation of the differences in effect produced by these compounds. For example, the frequency and duration of 'moving' dose-dependently increased after cocaine, while d-amphetamine and caffeine again produced bell-shaped dose-response curves. However, whereas low-intermediate doses of d-amphetamine reduced the mean duration of moving, sniffing and rearing, no such effect was observed at the highest dose tested. This finding, together with the appearance of licking in the behavioural repertoire, suggests a stereotyped character to responses seen at high doses of this compound, though neither cocaine nor caffeine induced stereotypy. As factor analyses also revealed quite different behavioural structures associated with these three drugs, present findings demonstrate that detailed observation of behaviour represents a useful approach to research on the behavioural pharmacology of psychostimulants.

Effects of amphetamine and apomorphine on locomotor activity after kainic acid lesion of the nucleus accumbens septi in the rat.

Kainic acid injections into the nucleus accumbens in rats induced severe loss of neuronal perikarya and the presence of gliosis in its vicinity, without affecting more distant areas. Spontaneous locomotor activity was elevated in the lesioned rats. After a low dose of d-amphetamine (1.5 mg/kg) no significant differences in locomotor activity were found between lesioned and sham-operated rats, while the increase in locomotor activity normally induced by a moderate dose of apomorphine (1 mg/kg) was blocked in lesioned rats. These results indicate that although dopamine receptors on the nucleus accumbens neurons are involved in the mechanisms mediating locomotor behaviour, the locomotor stimulant effect of d-amphetamine is not exclusively dependent on intra-accumbens dopaminergic activity.

Substance P injected into the region of the nucleus basalis magnocellularis facilitates performance of an inhibitory avoidance task.

The neuropeptide substance P (SP) was injected into the region of the nucleus basalis magnocellularis (NBM). The influence of SP on the performance of the single trial "uphill avoidance task" was tested. The post-trial injection of 1 ng SP (in 0.5 microliter volume) led to significantly longer latencies in the uphill response. This result can be interpreted in terms of a facilitating effect of SP on performance of an inhibitory avoidance response.

Turning behavior after unilateral lesion of the subthalamic nucleus in the rat.

Unilateral stereotaxic lesions of the subthalamic nucleus of rats with kainic acid induced a transient spontaneous ipsiversive turning which was present for several days, and which could be blocked by i.p. administration of haloperidol. After the 20th postoperative day, when no spontaneous turning activity was present, i.p. administration of apomorphine or amphetamine in the kainic acid lesioned rats induced ipsiversive turning, while i.p. haloperidol in the same rats induced contraversive turning. These findings suggest that the subthalamic nucleus is involved in the dopaminergic mechanisms mediating turning behavior of rats.

Differential alterations in basal and D-amphetamine-induced behavioural pattern following 6-OHDA or ibotenic acid lesions into the dorsal striatum.

It is well known that the corpus striatum is related to the sterotyped activation induced by several psychostimulants. In this study we analyzed the effects of 6-OHDA, in comparison with those of ibotenic acid lesions, into the dorsal striatum, on the behavioural pattern induced by saline or D-amphetamine treatment. A computerized technique for recording the animal motor activity was developed in order to define in a detailed way the behavioural profile in lesioned and sham-operated rats induced by the saline or D-amphetamine treatment. A 6-OHDA lesion into the dorsal striatum modified the basal behavioural pattern which was mainly characterized by reduced motor activation while ibotenic acid lesion affected the structure of the basal behavioral pattern. D-Amphetamine administration in 6-OHDA lesioned rats induced a behavioural stimulation, but a decreased motor and stereotyped activation was observed compared to the sham-operated animals treated with D-amphetamine. In contrast, D-amphetamine administration in the ibotenic acid-lesioned rats induced a motor and stereotyped activity which was not reduced compared to that seen after D-amphetamine treatment in sham-operated rats. These results suggest that these two types of lesion induced differential effects on the behavioural pattern either after saline or after D-amphetamine administration. Dopaminergic neurotransmission in the dorsal striatum plays a permissive role on the emergence of the behavioural responses, while the dorsal striatum circuitry plays a crucial role on the organization of the behavioural pattern. In addition, dopaminergic activity in this structure serves a primary control in the D-amphetamine-elicited motor activation or stereotypy, while the striatal structure is involved in the shaping of the D-amphetamine behavioural pattern.

Opposite rotation induced by dopamine agonists in rats with unilateral lesions of the globus pallidus or substantia nigra.

Normal rats with a unilateral ibotenic acid lesion of substantia nigra pars reticulata (SNR, n = 12) or globus pallidus (GP, n = 12) were challenged systemically with the mixed dopaminergic agonist apomorphine (0.5 and 1.5 mg/kg) and the indirect acting d-amphetamine (1.5 mg/kg). The low dose of apomorphine produced a weak contralateral rotation only in the SNR-lesioned group, which showed an intense ipsilateral rotation following the administration of the higher dose. GP-lesioned rats also showed ipsilateral rotation after the high dose of apomorphine. d-Amphetamine produced ipsilateral rotation in GP-lesioned rats, contrasting with a vigorous contralateral rotation in SNR-lesioned rats. The unexpected opposite rotation after apomorphine and d-amphetamine, observed only in SNR-lesioned animals, indicates that the role of SNR in basal ganglia functions is less clear and more complex than what is expected from our current model of basal ganglia circuitry and functions. On the other hand, the GP lesion resulted in a consistent and predictable ipsilateral rotation after both apomorphine and d-amphetamine, indicating a more determinant effect on the output of the basal ganglia than heretofore believed. Our results may contribute to the recently expressed views challenging the established model of basal ganglia organisation.

Topography of dopamine D-1 and D-2 receptor-mediated rotation after intrastriatal injections of dopamine-related drugs in normosensitive rats.

Naive rats were challenged systematically with apomorphine after receiving unilateral dorsal or ventral intracaudate injections of the dopamine D-1 receptor antagonist, SCH23390, or the D-2 receptor antagonist, sulpiride. Sulpiride injections into both the dorsal and ventral striatum induced a robust ipsilateral rotation, while SCH23390 elicited a weaker ipsilateral rotation only on injection into the ventral striatum. Both drugs were ineffective in saline-treated rats, although sulpiride injections into the ventral striatum after systemic saline elicited a small ipsilateral preference. The results from this rotational model mediated by normosensitive receptors indicate that only dopamine D-1 receptors in the ventral striatum mediate rotation while D-2 receptors in both striatal regions mediate rotation. A functional dichotomy between these two neostriatal regions is thus proposed.

The pattern of locomotor activity after cocaine treatment in the rat.

The present study used a computerised technique to assess the behavioural effects on locomotor activity of i.p. cocaine administration in the rat. This computerised method provides considerable information about various behavioural responses, as well as accuracy by measuring the frequency and duration of every behavioural event. Cocaine induced an increase in behavioural events related to motor activity, such as moving, sniffing and rearing, while standing was reduced. Cocaine increased the frequency of the behavioural responses recorded, but decreased their mean duration. No stereotyped behavioural element, such as head swinging, head bobbing, licking, stereotyped mouth moving or stereotyped sniffing, was recorded after cocaine treatment. Cocaine, unlike d-amphetamine, induced a specific behavioural pattern characterised predominantly at all doses by a stimulated motor activation involving an increase in moving and sniffing and a decrease in standing behaviour.

GABAergic mechanisms mediating rotational behavior in rats: differences between dorsal and ventral striatum.

Local injection of muscimol into the dorsal or ventral striatum of rats did not induce any rotational activity, but injection of picrotoxin into ventral striatal aspects induced an intense contralateral rotation. Amphetamine pretreatment resulted in an ipsilateral rotation after muscimol injection into dorsal striatum and in a complex rotational pattern after ventral injection, characterized by an initial short-lasting ipsilateral rotation followed by a long-lasting contralateral rotation. The contralateral rotation induced by picrotoxin was abolished by amphetamine pretreatment. These results indicate a functional heterogeneity between dorsal and ventral striatal mechanisms mediating rotational behavior, and a different pattern of dopamine-GABA interactions between dorsal and ventral striatum.

Behavioral effects of amphetamine and apomorphine after striatal lesions in the rat.

It is well established that denervation of the dorsal striatum by its dopaminergic afferents attenuates the stereotyped response to d-amphetamine, which can be considered as an extreme form of motor activation. However, it is difficult to sustain the view that this structure serves primary motor control function because the role of dopamine in the striatum remains difficult to understand. In this study, we compared the effects of two dopaminergic agonists, d-amphetamine and apomorphine, after dorsal striatal lesions with ibotenic acid using a computerized scoring of the behavior. Although d-amphetamine- and apomorphine-induced locomotor activity was no different between lesioned and nonlesioned rats in photobeam activity cages, the structure of their behavioral pattern was quite different. Freezing, a usual response after d-amphetamine, was blocked by the lesion. Lesioned rats exhibited less standing than nonlesioned after d-amphetamine, apomorphine, or saline treatment. Moving was increased in lesioned rats after a low dose of d-amphetamine (0.5 mg/kg) or apomorphine (0.5 mg/kg), while d-amphetamine induced in the same rats an increase of rearing. Stereotyped behavior after both drugs at high doses was not affected by striatal lesion. These results indicate that the dorsal striatum is not involved only in the control of stereotypy, as has been suggested using 6-hydroxydopamine lesions, but also plays a major role in the mediation of behavioral activation in response to stimulant drugs.

A comparative study of the behavioral effects of d-amphetamine and apomorphine in the rat.

A wide range of doses of d-amphetamine and apomorphine were injected into rats, in order to better characterize and compare dopaminergic agonist-induced behavioral effects. The study was carried out using a computerized technique for the quantification and analysis of various behavioral elements. Although both drugs increased motor activity and provided dose-dependent stereotyped responses, the whole pattern of behavior in the open field showed a different structure. d-Amphetamine in doses that did not produce stereotyped responses induced a wide range of varied behavioral elements with increased frequency but decreased mean duration, while apomorphine induced a more restricted behavioral profile. Furthermore, a higher frequency of freezing reaction was observed after d-amphetamine treatment in low doses but not after apomorphine treatment. Both drugs in high doses elicited a similar stereotyped syndrome characterized by repetitive movements of great duration, but at low doses the behavioral pattern was completely different. The apomorphine-induced syndrome was characterized mainly by moving and sniffing, interrupted by rearing, while the amphetamine-induced syndrome by sniffing and moving, interrupted by standing and freezing.

Effects of striatal or accumbens lesions on the amphetamine-induced abolition of latent inhibition.

In this study, we tested the effects of nucleus accumbens or corpus striatum lesions on the abolition of latent inhibition induced by d-amphetamine. In the latent inhibition paradigm, animals learn to ignore a repeatedly presented nonreinforced stimulus. In this paradigm, the repeated nonreinforced preexposure to a stimulus retards subsequent conditioning to that stimulus. Pharmacological manipulations that enhance the dopaminergic function (e.g., d-amphetamine) abolish this ability to ignore an irrelevant stimulus. Previous studies have revealed a major role of the nucleus accumbens in the d-amphetamine-induced abolition of latent inhibition because intraacumbens injections of the drug mimic its systemic effects. The results of this study, however, revealed a significant increase in the disruption of latent inhibition by d-amphetamine between corpus striatum-lesioned and sham-operated rats, but a marginal difference between nucleus accumbens lesioned and sham-operated rats, which had been preexposed to the stimulus. These findings indicate that the corpus striatum plays also a major role in the disruption of latent inhibition by d-amphetamine. It seems, therefore, that the nucleus accumbens and corpus striatum may represent a functionally common system regarding the expression of latent inhibition, although different experimental manipulation can favor the one structure over the other, reflecting probably their complex function.

Different patterns of rotational behavior in rats after dorsal or ventral striatal lesions with ibotenic acid.

Rats with total, dorsal or ventral ibotenic acid striatal lesions were challenged with DA agonists apomorphine and d-amphetamine. In rats with total lesions, both drugs induced an intense ipsilateral rotation, as did apomorphine in the dorsally lesioned rats. Amphetamine induced ipsilateral rotation in ventrally lesioned rats, but this effect may represent a non-specific potentiation of spontaneous ipsilateral rotation observed in this group. These results indicate that the neostriatum of the rat is not an homogeneous structure concerning the expression of rotational behavior after DA receptor stimulation.

Assessing personality traits by questionnaire: psychometric properties of the Greek version of the Zuckerman-Kuhlman personality questionnaire and correlations with psychopathology and hostility.

BACKGROUND: The Zuckerman-Kuhlman Personality Questionnaire (ZKPQ) was developed in an attempt to define the basic factors of personality or temperament. We aimed to assess the factor structure and the psychometric properties of its Greek version and to explore its relation to psychopathological symptoms and hostility features. METHODS: ZKPQ was translated into Greek using back-translation and was administered to 1,462 participants (475 healthy participants, 619 medical patients, 177 psychiatric patients and 191 opiate addicts). Confirmatory and exploratory factor analyses were performed. Symptoms Distress Check-List (SCL-90R) and Hostility and Direction of Hostility Questionnaire (HDHQ) were administered to test criterion validity. RESULTS: Five factors were identified, largely corresponding to the original version's respective factors. Retest reliabilities were acceptable (rli's: 0.79-0.89) and internal consistency was adequate for Neuroticism-Anxiety (0.87), Impulsive Sensation Seeking (0.80), Aggression-Hostility (0.77) and Activity (0.72), and lower for Sociability (0.64). Most components were able to discriminate psychiatric patients and opiate addicts from healthy participants. Opiate addicts exhibited higher rates on Impulsive Sensation Seeking compared to healthy participants. Neuroticism-Anxiety (p<0.001) and Impulsive Sensation Seeking (p<0.001) were significantly associated with psychological distress and Aggression-Hostility was the most powerful correlate of Total Hostility (p<0.001), and Neuroticism-Anxiety was the stronger correlate of introverted hostility (p<0.001), further supporting the instrument's concurrent validity. CONCLUSIONS: Present findings support the applicability of the Greek version of ZKPQ within the Greek population. Future studies could improve its psychometric properties by finding new items, especially for the Sociability scale.