Repeated apomorphine administration alters dopamine D1 and D2 receptor densities in pigeon basal telencephalon

When pigeons are repeatedly administered a dose of apomorphine they show an increasing behavioral response, much as rodents do. In birds this expresses itself in an augmented pecking response. This sensitization is assumed to be largely due to a conditioning process. Here we present evidence that sensitization is accompanied by an alteration of the D 1 to D 2 dopamine receptor densities. An experimental group of pigeons was repeatedly injected with apomorphine, and a control group with saline. The basal forebrain tissue, known to be rich in dopamine receptors, was subjected to binding assays using tritiated specific D 1 and D 2 dopamine receptor antagonists. There was a trend towards an increase in D 1 and a significant decrease in D 2 receptor densities in apomorphine-treated birds compared to the saline-treated controls. We conclude that extended apomorphine treatment modifies the D 1 dopamine receptor density in the opposite manner to the D 2 dopamine receptor density.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46541/1/221_2004_Article_2158.pd

It Takes a Village to Make a Scientist: Reflections of a Faculty Learning Community

Lab components of undergraduate science courses typically have students complete highly directed cookbook-like laboratory activities. These experiences rarely engage students in a meaningful manner and do not accurately convey what the work of science entails. With funding from the Howard Hughes Medical Institute (HHMI), we have created more authentic science research experiences in a variety of undergraduate science courses, including introductory courses. Achieving this among the diversity of freshmen and sophomore science courses—each typically serving hundreds of students on our campus—required careful planning and adaptation. This article describes the many challenges we faced in our effort to create more authentic undergraduate student research experiences and the significant progress we have made in making such experiences more common for our students. Improvements in first-year science, technology, engineering, and mathematics (STEM) retention over the last 2 years suggest that the experiences may be having a positive impact

It Takes a Village to Make a Scientist: Reflections of a Faculty Learning Community

Lab components of undergraduate science courses typically have students complete highly directed cookbook-like laboratory activities. These experiences rarely engage students in a meaningful manner and do not accurately convey what the work of science entails. With funding from the Howard Hughes Medical Institute (HHMI), we have created more authentic science research experiences in a variety of undergraduate science courses, including introductory courses. Achieving this among the diversity of freshmen and sophomore science courses—each typically serving hundreds of students on our campus—required careful planning and adaptation. This article describes the many challenges we faced in our effort to create more authentic undergraduate student research experiences and the significant progress we have made in making such experiences more common for our students. Improvements in first-year science, technology, engineering, and mathematics (STEM) retention over the last 2 years suggest that the experiences may be having a positive impact.This article is from Journal of College Science Teaching 44 (2015): 28. Posted with permission.</p

Die Rolle von Dopamin und Glutamat beim assoziativen Lernen der Taube (Columba livia)

Associative learning involves learning a connection between two events (two stimuli or a stimulus and a response) after their presentation so that the posterior occurrence of one of them activates the representation of the other. In the present dissertation, two associative learning paradigms are used in order to study the role of the glutamatergic and dopaminergic systems on learning. Apomorphine-induced learning and a simultaneous visual discrimination task are used to assess the participation of both systems mentioned above.Chapter I includes a brief introduction to learning (especially classical conditioning), the use of drugs and of contextual cues as stimuli in this domain. It also treats discrimination learning and colour preferences in birds and in animals in general. The two paradigms used in this work are briefly described in the context of dopamine and glutamate involvement. A brief introduction to dopaminergic and glutamatergic systems introduces the associative learning model proposed by Wickens (1990). This model will be used as a basis for the design and interpretation of the following experiments.Both the glutamatergic and dopaminergic systems in vertebrates are discussed in chapter II. A detailed description of the glutamatergic system is given and its relevance for the brain of vertebrates is analysed. Glutamate molecule synthesis and the most relevant glutamatergic process for learning, the long-term potentiation (LTP), are described. Further, a detailed description of the glutamatergic receptors as well as a general view of their participation in the different glutamatergic pathways are revised. Special emphasis falls on the NMDA glutamate receptor (an ionotropic channel receptor). Because of its critical role in learning, the corticostriatal glutamatergic pathway together with the remaining glutamatergic pathways is described. The hypothetical involvement of LTP in learning is discussed. Also a description of dopamine action mechanisms on

Behavioral sensitization to apomorphine in pigeons (Columba livia) : blockade by the D₁ dopamine antagonist SCH-23390

Repeated administration of apomorphine leads to a context-dependent pecking response sensitization. Previously sensitized pigeons (Columba livia) challenged with saline in the same context show a conditioned response (CR). The authors studied the effects of intrastriatal injections of the dopamine (D₁) antagonist SCH-23390 on both the sensitized response and the CR. When coadministered with apomorphine, SCH-23390 inhibited the initial response to apomorphine, prevented the development of sensitization, and impaired the maintenance of an already developed sensitization. However, SCH-23390 had no effect on the retrieval of a previously established CR. It is concluded that the activation of D₁ receptors in the caudal avian striatum is necessary for the acquisition and maintenance of the sensitization, but not for the expression, of the CR

Apomorphine and psychostimulant addiction

Apomorphin wurde Mitte des 19. Jahrhunderts ausgehend von Morphium hergestellt. Gleich nach der Synthese fiel dessen emetische Wirkung auf. Eine analgetische und euphorisierende Wirkung wie Morphium hatte es nicht. Klinisch ist es dann in höheren Dosen bei Vergiftungen und später auch zeitweise bei der Alkoholaversionstherapie verwendet worden. Tierversuche haben aber dann gezeigt, dass es in niedrigeren Dosen auffällige orale Stereotypien auslöst. Bei Kröten und Fischen sind das Schnappanfälle, bei Tauben und Hühnern Putz- und Pickanfälle und bei Ratten und Mäusen Kau- und Nageanfälle. Auch bei Menschen werden u. U. Kaustereotypien beobachtet. In den 50er Jahren wurden bei Ratten und Mäusen Ähnlichkeiten mit der Wirkung von Psychostimulanzien, insbesondere Amphetamin und Kokain, erkannt. Labortechnisch äußert sich das nicht zuletzt dadurch, dass es nach Gaben dieser Drogen und Apomorphin bei den Nagern neben den Stereotypien zu nachhaltigen, leicht messbaren Laufaktivitätssteigerungen in Aktometern kommt. Dadurch, dass Amphetamin und Kokain als Dopaminagonisten erkannt wurden, unter anderem weil sie bei wiederholter Einnahme zu psychoseähnlichen Symptomen führten und Schizophrenie wiederum als eine Hyperdopaminie angesehen wurde, kam es zur Feststellung, dass Apomorphin ebenfalls ein Dopaminagonist sei. Der beste Beweis dafür ist, dass Haloperidol, der klassische Dopaminantagonist, sehr effizient die pharmakologische Wirksamkeit von Apomorphin zu unterbinden vermag. Inzwischen ist es nachgewiesen, dass sich Apomorphin direkt und spezifisch an die Dopaminrezeptoren der D 1 und D2 Familien bindet und dies mit einer Effektivität, die die des Transmitters Dopamin um etwa das Tausendfache übersteigt. Das ist auch ein Grund, warum Apomorphin, allerdings meistens nur vorübergehend, in der Parkinsontherapie verwendet wird. Neuerdings soll es in niedrigen posen als männliches Sexualstimulantium, welches vielleicht Viagra ausstechen kann, vermarktet werden. Kokain und Amphetamin sind im Gegensatz zu Apomorphin indirekte und nicht ganz so spezifische Agonisten des Dopamins, wobei die erste Substanz vornehmlich den Rücktransport des Transmitters aus dem synaptischen Spalt in die präsynaptischen Endigungen blockiert und die zweite Substanz vornehmlich eine vermehrte Ausschüttung von Dopamin aus den präsynaptischen Endigungen fördert. Inwieweit die direkten sehr spezifischen und die indirekten eher unspezifischen Wirkungsweisen der Drogen damit zu tun haben, dass Apomorphin gar nicht, aber Amphetamin und Kokain suchtauslösend wirken, wird noch zu kommentieren sein

Sensitization to apomorphine, effects of dizocilpine NMDA receptor blockades

The dopamine agonist apomorphine (apo) elicits bouts of stereotyped pecking in pigeons, a response which increases with successive apo injections. This sensitization is strongly context-specific and has been suggested to arise through a Pavlovian conditioning to both external and internal cues. We hypothetized that this learning involves dopamino–glutamatergic interactions and investigated the issue by inducing NMDA glutamate receptor blockades with the antagonist dizocilpine (diz). A first experiment examined the effects that four different doses (ranging between 0.05 and 0.12 mg/kg) of diz co-administered with a standard dose of 0.5 mg/kg of apo had on the development of the incremented response and on the later expression of the conditioned pecking response. Both responses were impaired by doses of around 0.10 mg/kg diz. A second experiment assessed whether either a diz treatment or a diz plus apo co-treatment affected the development of a subsequent sensitization to apo. The first treatment had no effect on the latter sensitization. A part sensitization that arose with the second treatment did not transfer to the final sensitization. The last experiment examined whether the administration of diz had an immediate effect on the incremented responding to apo and on the conditioned response shown by already sensitized pigeons. No effect was apparent with the first treatment, but there was a marked response inhibition with the second treatment. It is concluded that NMDA glutamate receptors play an important role in apo-induced sensitization in pigeons which is compatible with the Pavlovian conditioning account of sensitization