The role of dopamine D3 receptor in the amphetamine-induced conditioned place preference in mice / 法医学杂志

OBJECTIVE@#To study the role of dopamine D3 receptor involved in the amphetamine-induced conditioned place preference (CPP) in mice.@*METHODS@#The CPP was observed in D3 receptor knock-out (D3RKO) mice and C57BL/6 wild-type control mice after administration of amphetamine. The data were analyzed with a two-way ANOVA using the SPSS 13.0 software.@*RESULTS@#D3RKO mice showed a significant amphetamine-induced CPP (P<0.001), compared with the ones administered with saline in C57BL/6 control mice.@*CONCLUSION@#The results indicate that amphetamine can produce significant CPP in dopamine D3 receptor knock-out mice, suggesting that amphetamine-induced addiction can be inhibited by dopamine D3 receptor.

Analgesia in phasic and tonic pain tests in a pharmacological model of autotomy.

Self-mutilation or self-injurious behaviour is a well known behavioural disorder in humans. The proposition that this behaviour in animals is a response to chronic pain of peripheral nerve injury has been met with controversy. In the present study a pharmacological model, which produces no sensory or motor loss was used to study how autotomy is related to pain. In a group of rats autotomy was induced by amphetamine in phenoxybenzamine and reserpine treated animals. The pain tests, both phasic and tonic were then performed. The results of this study showed that a total analgesia was produced in both phasic and tonic pain tests, in animals that exhibited autotomy. Injection of naloxone in these animals prevented autotomy. A correlation between autotomy and no pain is suggested in this pharmacological model of autotomy.

Hacia una comprensión de las bases biológicas de la conducta / Toward understanding the biological bases of behavior

En este trabajo se exponen algunos de los desarrollos más recientes en el estudio de las bases biológicas de la conducta, a partir de la obra de Arvid Carlsson, Paul Greengard y Eric Kandel. Se analiza el descubrimiento del mecanismo de acción de los neurolépticos y la situación actual de la hipótesis dopaminérgica de la esquizofrenia. Luego se revisan algunos aspectos del estudio de las bases biológicas de la memoria, en especial las bases genéticas del aprendizaje y la memoria. Por último, se analizan los nuevos conceptos acerca de la relación entre cerebro y conducta y de los determinantes genéticos y ambientales en las enfermedades mentales. Se concluye que los progresos de la neurobiología moderna han modificado profundamente la psiquiatría, acentuando su carácter de especialidad médica y volviendo a acercarla a la neurología

Quantification of behaviour in social colonies of rhesus monkey.

It is necessary to use experimental animals with behavioural, physiological and disease susceptibility pattern similar to man so that the results have a clinical predictive value. For such studies the non-human primate is the animal of choice. Rhesus monkey is a good choice for this purpose but information about its behaviour is fragmentary. In order to obtain a quantitative baseline data for psychopharmacological studies, a protocol has been developed to score various social and solitary behaviours in adult male and female rhesus monkeys. The study was conducted on rhesus monkeys in a social colony of one male and seven female living in a semi-restricted environment. The behavioural patterns were quantitated so as to compare effect on various components of behaviour. Aggressiveness and vigilance were prominent in the male while social affiliative behaviour was dominant in the female. Other behavioural responses were of similar magnitude in both sexes. It is however necessary to have data with some standard CNS active agents on these behavioural protocol. Therefore, initially the behavioural effects of amphetamine and haloperidol were studied. Significant effects observed following d-amphetamine (1-4 mg/kg, im); it induced dose dependent suppression of social behaviour (approach, contact, grooming), feeding, hypervigilance, stereotypy and oral hyperkinesia. On the other hand haloperidol (0.01-0.04 mg/kg, im) produced decrease in social and solitary behaviour and marked cataleptic posture. It is possible to quantitate drug effects on various aspects of behaviour of the rhesus monkey and to develop neuropsychitric models with the help of this protocol for use in study of drug effects on behaviour.

Quantitative assessment of amphetamine induced behavioural changes in rhesus monkeys, Macaca mulatta.

Graded dose of amphetamine (AMP; 1-4 mg/kg, im) induced suppression of approach, contact, body jerk, grooming and food forage, hypervigilance (checking), stereotyped behaviour and oral hyperkinesia in rhesus monkeys. Pretreatment with haloperidol--a dopamine receptor blocking agent (0.04 mg/kg, im)--significantly suppressed the AMP induced hypervigilance, stereotypy and oral hyperkinesia but was unable to reverse other AMP induced behavioural effects in the monkeys. Haloperidol (0.01-0.04 mg/kg, im) per se produced decrease in social and solitary behaviour and marked cataleptic posture. The results suggest that dopamine may be playing an important role in the mediation of many AMP induced behavioural changes in primates.

Effect of apomorphine on rat motor activity induced by fencamfamine and other indirect psychostimulant drugs

We evaluated the effects of low doses of apomorphine on the stimulant behavioral effects induced by amphetamine (2.5 mg/Kg), fencamfamine (6.0 mg/Kg) and cocaine (15,0 mg/Kg). Rats received 0.02 mg/Kg of apomorphine (sc) and 30 min later were injected with one of the stimulants.Motor activity including locomotion, rearing and sniffing was quantified in the animals home cages for 60 min at 15-min intervals. All stimulant drugs induced hyperactivity. When apomorphine was administered before cocaine, but not when administered before fencmfamine or amphetamine, distinctive changes occurred. The behavioral pattern resulting from high stimulation was replaced by that related to low stimulation, suggesting that apomorphine induces a transfer in the predominant behvior in cocaine-, and partially in fencamfamine-, but not in amphetamine-treated animals, by decreasing the intensity of the stereotyped effect. While no changes occured when apomorphine was administered before amphetamine, the fencamfamine group showed intermediate alterations (nonsignificant changes in sniffing but a significant increase in rearing behavior). These results are discussed in terms of the different mechanisms of presynaptic action of the drugs studied

Parasympatholytic activity of psychoactive drugs in rat brain mitochondria.

Chlorpromazine, imipramine and amphetamine at a concentration of 0.66, 1.33 and 13.3 x 10(4) M in vitro inhibited acetyl cholinesterase activity by 16, 23 and 31% respectively in rat brain mitochondria. No change in enzyme activity was induced by these drugs in vivo. There is little cholinergic facilitation through acetylcholinesterase inhibition in the presence of psychoactive drugs.

Pharmacodynamic interactions of cypermethrin and centrally acting drugs in mice.

Cypermethrin a widely used insecticide of Pyrethroids (type II) group, was administered in mice at two dose levels (1/10 of LD50 i.e. 2.5 mg/kg and 1/5 of LD50 i.e. 5.0 mg/kg) and pharmacodynamic interactions of insecticide were studied with centrally acting drugs viz. pentobarbital sodium, amphetamine, pentylenetetrazole, acepromazine and analgin. Cypermethrin pretreatment potentiated the actions of pentobarbital and pentylene-tetrazole as evidenced by an increase in pentobarbital induced hypnosis and duration of pentylene-tetrazole induced chemoshock seizures. Tranquilizing action of acepromazine was potentiated but there was decrease in amphetamine influenced locomotor activity at both the dose levels. Cypermethrin pretreatment, however, did not have any pharmacodynamic interaction with analgin.

Role of opioid receptors in self-aggression in rats.

Self-aggression is a behavioural disorder in which an individual damages its own body parts by intense biting or scratching. Self aggression has been reported in human patients in Lesch-Nyhan syndrome and in cases of schizophrenia, depression, and congenital analgesia. In human patients as well as in experimental animals some kind of dysesthesia of the part of the body that is mutilated has been suggested. This study was conducted to find out the underlying pain mechanisms in self-aggressive behaviour arising out of stereotypy. The study was performed in 40 adult male rats. In all these animals, self-aggression was produced as part of amphetamine induced stereotyped behaviour. A predetermined scale was used for quantifying this behaviour. Reserpine and phenoxybenzamine pretreatment led to an increase in the incidence of self-aggression. Naloxone administration in reserpine pretreated animals led to a further significant increase in the incidence of self biting as compared to controls. From these studies it appears that self-aggressive behaviour may be associated with increased pain sensation.

Physical and behavioral development in rats after late prenatal exposure to diazepam.

The effect of late prenatal exposure to diazepam (DZP) on physical and behavioral development of rat pups was investigated. Prenatal exposure to DZP (20 mg/kg, sc, in last week of pregnancy) did not alter litter size and no gross malformations were noted at birth. Body weight at birth and subsequent weight gain was significantly less in these animals. The development of reflexes and neuromuscular maturation was normal. Open field locomotor activity and rearing scores were significantly decreased. Test of social play in juvenile rats revealed normal pattern of sexual dimorphism with increased masculinized behavior. Acquisition and retention of passive avoidance task was not affected by DZP exposure, however, retention of brightness discrimination task was significantly decreased. The hypnotic effect of a challenge dose of DZP and convulsive effect of pentylene tetrazole remained unaltered. Open field activity test in adult animals revealed increased ambulation. Probe dose of amphetamine in these animals caused paradoxical decrease in activity. It is concluded that exposure to high dose of DZP during late prenatal period may not manifest in physical or neuromuscular impairment during early development period, except for weight loss, however, it may have long term effects on behavior becoming manifest in adolescence and at maturity.

Efeitos comportamentais de apomorfina e d-1 anfetamina no gerbil (Meriones unguiculatus) / Behavioural effects of apomorphine and d-1 amphetamine in gerbils (Meriones unguiculatus)

Objetivou-se estudar os efeitos comportamentais da apomorfina HC1 (0,3 a 20mg/kg i.p.) e sulfato de d-1 anfetamina (0,3 a 10 mg/kg i.p.) no gerbil. A apomorfina e a anfetamina näo induziram consistente farejar, lamber ou morder estereotipados. Os efeitos mais evidentes da apomorfina foram o verticalizar, os episódios de imobilizaçäo e o "comportamento explosivo" (hiper-reatividade como correr desenfreado e saltos). A anfetamina, por outro lado, produziu limpeza da face, salivaçäo excessiva, piloereçäo, "esparramar" e hiperatividade motora. As duas drogas diminuíram o levantar sem apoio. A apomorfina diminuiu e a anfetamina elevou a temperatura coporal do%temperatura corporal do gerbil. Os resultados säo discutidos comparativamente com o que foi publicado em relaçäo a outros roedores

Teoría dopaminérgica de la esquizofrenia una revisión crítica / Dopaminergic theory of the schizophrenia. A critical review

Se hace una revisión de la literatura acerca de la llamada hipótesis dopaminérgica de la esquizofrenia. Las evidencias a favor y en contra de los mecanismos dopaminérgicos en la esquizofrenia son analizadas separadamente en dos hipótesis potencialmente relacionadas, la del bloqueo de la dopamina y la de la sobreactividad de las acciones dopaminérgicas. En adición se discuten otras hipótesis alternativas derivadas de las anteriores. Se concluye en que aparentemente no existe, a pesar de las cuidadosas investigaciones descritas, un agente etiológico que en forma individual pueda causar la esquizofrenia

A comparative study of several methods for recording spontaneous motor activity in mice under drug effects.

Various existing methods of recording motor activity in animals are briefly reviewed. An electronic adaptation of an old one, the Jiggle cage, is described. The relative advantages and demerits in recording behaviour of mice under drug effects are compared with those of the traditional Jiggle cage, an electromagnetic activity counter and observational ratings.