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

Serotonin and conditioning: Focus on Pavlovian psychostimulant drug conditioning

“…In our most recent studies, we have shown that repeated pairing of the D1/D2 agonist apomorphine, at dose levels that elicit hyper-locomotion with placement in an open-field, generates both context specific cue conditioned hyper-locomotion and context specific sensitized drug induced hyper-locomotion effects [47,49,51,85]. In line with the extant literature, extinction eliminates the conditioned apomorphine hyper-locomotion response but not the sensitized apomorphine hyper-locomotion response.…”

“…In contrast to many drugs that induce tolerance effects, the repeated use of psychostimulants induce sensitization and conditioned drug effects that enhance the drug effects [42][43][44][45][46][47][48][49][50][51]. In terms of Pavlovian conditioning, psychostimulant drugs are administered to animals by an experimenter independent of the animal's behavior and therefore serve as unconditioned stimuli that elicit unconditioned drug responses.…”

Enhanced antinociception with repeated microinjections of apomorphine into the periaqueductal gray of male and female rats

“…This enhanced apomorphine potency occurred in both male and female rats and is in direct contrast to the rapid decrease in morphine potency with repeated administration (Morgan et al, 2006, Bobeck et al, 2012). Although the neural mechanism for antinociceptive sensitization to apomorphine is not known, it is consistent with the behavioral sensitization that can occur with repeated administration of psychostimulants (Kalivas et al, 1993, Braga et al, 2009). Sensitization to apomorphine-induced antinociception could potentially be exploited therapeutically if dopamine receptors can be targeted specifically and in the absence of side effects.…”

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

“…At this time, the high apomorphine dose would activate the dopamine system and maintain the cue/dopamine association whereas the low dose apomorphine would shut down the dopamine system and severely diminish the cue/dopamine association to even a greater degree than the vehicle treatment resulting in the subsequent behavioral inhibition observed on the next exposure to the test environment. Previously, we have used the same low dose apomorphine treatment in a conventional paired/unpaired Pavlovian protocol and found either no conditioning or weak conditioning to test environment cues of the pronounced response inhibition induced by repeated low dose apomorphine treatments (Braga et al 2009a). In a way, our previous findings (Braga et al 2009a) are consistent with the important role generally ascribed to dopamine in conditioning in that the low dose apomorphine treatment that suppressed dopamine and consequently cue salience was ineffective in generating conditioned behavioral inhibition despite the elicitation of a strong unconditioned behavioral inhibitory response.…”

“…Previously, we have used the same low dose apomorphine treatment in a conventional paired/unpaired Pavlovian protocol and found either no conditioning or weak conditioning to test environment cues of the pronounced response inhibition induced by repeated low dose apomorphine treatments (Braga et al 2009a). In a way, our previous findings (Braga et al 2009a) are consistent with the important role generally ascribed to dopamine in conditioning in that the low dose apomorphine treatment that suppressed dopamine and consequently cue salience was ineffective in generating conditioned behavioral inhibition despite the elicitation of a strong unconditioned behavioral inhibitory response. Unlike a treatment that activates the dopamine system and increases stimulus salience, a dopamine autoreceptor treatment shuts down the dopamine system and blunts stimulus salience.…”