A partial habituation method to test for anterograde and retrograde amnestic treatment effects: Evidence that antagonism of the NMDA receptor can induce anterograde but not retrograde amnestic effects.

Background: A progressive decrease in spontaneous locomotion with repeated exposure to a novel environment has been assessed using both within and between-session measures. While both are well-established and reliable measurements, neither are useful alone as methods to concurrently assess treatment effects on acquisition and retention of habituation.

New Method: We report a behavioral method that measures habituation by combining the within and between measurements of locomotion.

Post-trial dopaminergic modulation of conditioned catalepsy: A single apomorphine induced increase/decrease in dopaminergic activation immediately following a conditioned catalepsy response can reverse/enhance a haloperidol conditioned and sensitized catalepsy response.

Haloperidol can induce catalepsy and this drug effect can be conditioned as well as sensitized to contextual cues. We used a paired/unpaired Pavlovian conditioning protocol to establish haloperidol catalepsy conditioned and sensitized responses. Groups of rats were given 10 daily catalepsy tests following administration of vehicle (n=24) or haloperidol (1.

Reciprocal activation/inactivation of ERK in the amygdala and frontal cortex is correlated with the degree of novelty of an open-field environment.

Rationale: Phosphorylated extracellular signal-regulated kinase (ERK) has been used to identify brain areas activated by exogenous stimuli including psychostimulant drugs.

Objective: Assess the role of the amygdala in emotional responses.

Methods: Experimental manipulations were performed in which environmental familiarity was the variable.

Increase in medial frontal cortex ERK activation following the induction of apomorphine sensitization.

Repeated high dose injections of the direct acting D1/D2 agonist apomorphine (APO) induces context specific behavioral sensitization. We assessed the effects of 2.0 mg/kg APO on open-field locomotor responses of rats over a 30 min period following either single or five daily APO injections.

Drug memory substitution during re-consolidation: a single inhibitory autoreceptor apomorphine treatment given during psychostimulant memory re-consolidation replaces psychostimulant conditioning with conditioned inhibition and reverses psychostimulant sensitization.

Psychostimulant conditioning and sensitization effects have proven to be difficult to eliminate using behavioral methods. We used a low autoreceptor dose of apomorphine in counter-conditioning and memory re-consolidation protocols to modify conditioned and sensitized responses induced by a high dose of apomorphine. Rats received five daily treatments of apomorphine (2.

Opposite effects of typical and atypical anti-psychotic drugs on sensitized dopamine receptors: sub-chronic low dose Olanzapine exposure reverses sensitization but a similar regimen of low dose haloperidol potentiates sensitization effects.

Rationale: Both typical and atypical antipsychotic drugs are D2 receptor antagonists but yet appear to have markedly different effects upon the induction of dopamine sensitization.

Objective: This study aims to compare the effects of subchronic regimens of low-dose olanzapine and haloperidol administered to rats previously sensitized to apomorphine.

Methods: Initially, rats received apomorphine (2.

Residual dopamine receptor desensitization following either high- or low-dose sub-chronic prior exposure to the atypical anti-psychotic drug olanzapine.

Rationale: Anti-psychotic drugs are antagonists of dopamine D2 receptors and repeated administration may lead to the development of dopamine receptor supersensitivity.

Objectives: The objective of this study is to investigate the effects of sub-chronic olanzapine treatments upon the induction of dopamine receptor supersensitivity.

Methods: Rats were administered ten daily low or high doses of the atypical anti-psychotic drug olanzapine (0.

Post-trial apomorphine at an autoreceptor dose level can eliminate apomorphine conditioning and sensitization: support for the critical role of dopamine in re-consolidation.

Re-exposure to conditioned drug stimuli triggers re-consolidation processes. In the present study post-trial apomorphine treatments were administered in order to interact with the re-consolidation of an apomorphine conditioned/sensitized locomotor response. A low (0.

Opposite effects of low versus high dose haloperidol treatments on spontaneous and apomorphine induced motor behavior: evidence that at a very low dose haloperidol acts as an indirect dopamine agonist.

Anti-psychotic drugs are antagonists at the dopamine D2 receptors and repeated administration can lead to the development of dopamine receptor supersensitivity. In two experiments, separate groups of rats were administered 10 daily low or high doses of the typical anti-psychotic drug haloperidol (0.03 or 1.

Memory re-consolidation and drug conditioning: an apomorphine conditioned locomotor stimulant response can be enhanced or reversed by a single high versus low apomorphine post-trial treatment.

Rationale: Psychostimulant sensitization can have transformative effects upon contextual stimuli such as acquired conditioned stimuli and conditioned incentive motivational properties.

Objective: The aim of this study is to induce apomorphine sensitization and conduct non-drug exposures to the contextual cues followed by post-trial treatments designed to associate increases/decreases in dopamine activity with re-consolidation of the contextual cue conditioned stimulus.

Methods: Separate groups received five daily apomorphine (2.

Reversal of apomorphine locomotor sensitization by a single post-conditioning trial treatment with a low autoreceptor dose of apomorphine: a memory re-consolidation approach.

Sensitization is a common feature of psychostimulants and sensitization effects are generally considered to be linked to the addictive properties of these drugs. We used a conventional paired/unpaired Pavlovian protocol to induce a context specific sensitization to the locomotor stimulant effect of a high dose of apomorphine (2.0mg/kg).

Apomorphine-induced context-specific behavioural sensitization is prevented by the D1 antagonist SCH-23390 but potentiated and uncoupled from contextual cues by the D2 antagonist sulpiride.

Rationale: In the study of behavioural sensitization induced by dopamine agonists, D1 and D2 receptors have a critical, but a puzzling role.

Objective: The objective of this study is to examine the effects of the D1 antagonist SCH-23390 and the D2 antagonist sulpiride given repeatedly alone or in combination with apomorphine upon apomorphine conditioning and sensitization.

Methods: Apomorphine-induced (2.

Behavioral sensitization to dopaminergic inhibitory and stimulatory effects induced by low vs. high dose apomorphine treatments: an unconventional dose and response reversal sensitization challenge test reveals sensitization mechanisms.

Low dose apomorphine treatments preferentially activate dopamine autoreceptors and inhibit dopamine neurons as well as behavior. In contrast, high doses of apomorphine induce locomotor stimulation by activating dopamine postsynaptic receptors. We compared the effects of low (0.

Low dose apomorphine induces context-specific sensitization of hypolocomotion without conditioning: support for a new state dependent retrieval hypothesis of drug conditioning and sensitization.

High doses of apomorphine induce sensitization to locomotor stimulant effects whereas low doses induce locomotor inhibition. We examined whether repeated low dose apomorphine induced sensitization and conditioning to the locomotor inhibitory effect. Three doses of the D1/D2 agonist, apomorphine, were used in a Pavlovian conditioning protocol: 0.

Conditioned locomotion induced by unilateral intrastriatal administration of apomorphine: D(2) receptor activation is critical but not the expression of the unconditioned response.

The present study examined the role of D(1) and D(2) receptors in the conditioning of apomorphine-induced locomotor behavior. A Pavlovian conditioning protocol was used in which rats received 5 daily intrastriatal apomorphine treatments paired or unpaired to an open-field environment followed, 2 days later, by a saline test for conditioning. In the conditioning induction phase, the intrastriatal apomorphine treatment increased locomotor activity expressed as an increased number of sectional crossings and rearings.