Cognitive effects of dopaminergic and glutamatergic blockade in nucleus accumbens in pigeons.

In earlier studies it was found that glutamatergic transmission within the nucleus accumbens septi is involved in the performance of a learned visual shape discrimination in pigeons. This study examines what effects several kinds of glutamate and dopamine antagonists have on the same task. Pigeons were trained with the relevant discrimination, bilaterally implanted with cannulas into the nucleus accumbens and tested after various transmission blockers had been administered intracerebrally. SCH-23390, a D1 dopamine antagonist, at the dose used, had no effect, and Spiperone, a D2-dopamine and 5HT2a-serotonine antagonist, significantly decreased the error repeat trials. CNQX, a non-NMDA glutamate receptor antagonist, and Cycloleucine, an antagonist of the glycine allosteric site of NMDA receptors, had no effect. CGS-19755, a selective competitive NMDA antagonist, significantly impaired performance by significantly decreasing the percent correct trials and increasing the error repeat trials. CPPG, a II/III metabotropic glutamate antagonist, remarkably improved performance. MMPG, a III/II metabotropic glutamate antagonist, at the dose used, did not have any significant effect. The preparation employed may be a useful animal model of perceptual disturbances in schizophrenia.

Haloperidol blocks the acquisition but not the retrieval of a conditioned sensitization to apomorphine.

The dopamine agonist apomorphine (apo) elicits stereotyped pecking bouts in pigeons, a response which increases with successive apo injections. The present study sought, first, to confirm the hypothesis that this sensitization arises through a Pavlovian conditioning driven by both external and internal cues; and, secondly, to advance the hypothesis that during this learning the dopaminergic activation only initiates a process that probably ends in glutamatergic synapse modifications. The conditioned nature of the sensitization to apo was examined in two separate experiments that compared context contingent and context uncontingent apo treatments. The role of dopaminergic mechanisms in the acquisition, maintenance and retrieval of sensitization-conditioned pecking was examined by administering the dopamine antagonist haloperidol (hal) either before, during or after apo sensitization treatments. A contingency between context and apo was found to be essential for the acquisition and retrieval of apo-sensitized pecking. A pretreatment with hal did not curtail a subsequent sensitization to apo. When hal was co-administrated with apo it suppressed the initial pecking response to apo and blocked the acquisition of sensitized responding. A pecking response normally observed when apo-sensitized pigeons are challenged with saline (sal) in the same cage in which they were sensitized, was also absent. When hal was co-administered with apo after the sensitization was complete this led at first to an only partial apo response suppression. When treated with hal in the same cage, already sensitized pigeons responded much as if they had been challenged with sal. The sensitization induced by apo was thus blocked by hal co-administered during acquisition, but during the maintenance or retrieval phase hal did not impair a previously sensitized responding. It is concluded that when pigeons are sensitized to apo, dopaminergic mechanisms are implicated in initiating the neural modifications that underlie the conditioned sensitization, but that they themselves are not importantly altered.

Catecholaminergic and dopamine-containing neurons in the spinal cord of pigeons: an immunohistochemical study.

Within the different species belonging to the vertebrate radiation, catecholaminergic elements of the spinal cord present a partly conservative, partly variable pattern. Unfortunately, the overall picture is far from clear since the situation for birds is largely obscure. Therefore, we examined the distribution of dopamine (DA)- and tyrosine hydroxylase (TH)-positive cells and fibers in the spinal cord of the adult pigeon by immunohistochemistry. TH-immunoreactive cells were located within two restricted areas. One group of cells with multipolar shape was located in laminae VI and VII, close to the white-gray border. These cells were more frequently found at rostral and caudal levels while being scarce at cervical-thoracic levels. The second group of cells was located in lamina VIII surrounding the central canal. These cells were bipolar in shape and were found ventrally and laterally to the central canal, with most of them contacting the lumen of the canal through a separate process. The TH-immunoreactive fibers were distributed in both the gray and the white matter. In the gray matter, they were mainly distributed around the central canal (lamina VIII), in the ventral horn close to the border of laminae VII-IX and in the lateral part of the dorsal horn in laminae II-VI. In the white matter the fibers were present in the lateral columns running longitudinal to the main axis. DA-immunoreactive cells were also located within two restricted areas, closely matching the distribution of TH-immunopositive ones. Additionally, the DA-immunoreactive cells had the same shape as the TH-immunoreactive cells, as bipolar neurons contacted the central canal and multipolar ones were located in the laminae VI and VII. Also the distribution of DA- and TH-immunoreactive fibers roughly matched. Both, DA-immunoreactive cells and fibers were scarcer than TH-immunoreactive ones. This finding suggests that the catecholaminergic system in the spinal cord consists of DA-immunoreactive cells as well as other catecholaminergic cells.

Apomorphine sensitization: evoking conditions, context dependence, effect persistence and conditioned nature.

When repeatedly administered a dose of apomorphine (Apo), pigeons, much like rodents, show behavioural sensitization. In birds this sensitization expresses itself as an increasing pecking response to the drug and is found to be partially dependent on the environmental context in which Apo takes effect. In the first experiment we examined what effect different inter-Apo administration intervals have on the development of Apo sensitization and found that, with some smaller variations, intervals between 3 hours and 5 days all yielded comparable courses of sensitization. In the second experiment we examined how long pigeons had to be exposed to the same distinct cage to reveal a maximal context-dependent sensitization. Pigeons were therefore repeatedly injected with Apo and consistently placed in an experimental cage for different lengths of time (5 to 60 min; the overall drug effect lasted for about 1 h) before being returned to their standard home cages. Subsequent tests in the experimental cage and a standard cage showed that 20-min post-injection exposures were sufficient to yield a maximal response in the experimental cage. After training with 20- and 60-min exposures, the pigeons pecked about three times more in the experimental cage than in the standard cage. This confirmed the marked context dependency of the sensitization effect. In the third experiment, groups of pigeons were injected repeatedly with Apo and directly afterwards placed either consistently into the same experimental cage or into different experimental cages. The same-cage group evidenced a significantly much stronger sensitization than the different-cage group. A cage-habituation group served as a control for the possibility that the weaker sensitization of the different-cage group might be due to a cage novelty effect. This cage-habituation group was run under the same conditions as the different-cage group but with additional exposures to the crucial cage while injected with saline. This extra treatment did not augment the pecking response to Apo in that cage. In the fourth experiment we examined how long the sensitization to Apo lasts and found that, even after 2 years of drug abstinence, it only waned to 50% of the original asymptotic response. The overall results support the hypothesis that a very major part of the sensitization to Apo in pigeons is due to a conditioning to the environmental context and to the drug state itself.